Tag Archives: brain

Junk Food | The Paleo Diet

While the title of this article may at first seem implausible (and somewhat scary), a new scientific study seems to show that an inborn preference for junk food is not only possible – it may be affecting more of us than ever could have possibly been imagined. For the first time in history, researchers for Obesity Society have identified two genetic variants, which help to change how the brain responds to high-calorie foods.1 2 While this is potentially terrible news for those of us who struggle to resist highly processed and manufactured foods – it also means there is possibly a way to stop this genetic variant from controlling our dietary choices. This could include changing how the brain processes junk food, changing how much people crave these foods, and even altering the brain’s dopamine system. There are even more potential treatments using this new information – including using gut hormones to act on dopamine brain cells.

To delve into further detail, researchers specifically found that two genetic variants – FTO and DRD2 – influenced brain activity related to the reward system. This occurred when subjects simply looked at pictures of high-calorie foods. As I’ve written previously, this is far from the first time neuroscience (or other scientific studies) have shown that some of our brains respond differently, to rewarding foods.3 4 5 6 7 8 9 10 11 In early 2014, for example, a study was published which showed that not only did some people crave chocolate (while others did not) – but that there was literally different brain activity, in the two groups.12

Asmaro D, Liotti M. High-caloric and chocolate stimuli processing in healthy humans: an integration of functional imaging and electrophysiological findings. Nutrients. 2014;6(1):319-41.

In another, similar study, researchers found that by altering dopamine receptors (specifically D2 receptors) – they could cure binge eating.13 Unfortunately for us, that ground breaking study was done on rats – not humans. However, this is further evidence that our brain plays a fundamental role in overeating and cravings. In fact, it may be the excess stimulation of the nucleus accumbens (the ‘pleasure center’ of the brain) from junk food, which leads to obesity.14 15 16 17 18 19 20

How does this relate to our current world? Well, 70% of the United States is overweight, with 30% of us now being obese.21 What accounts for all these extra pounds? Certainly, as shown by research from Yale scientists, a hyper-stimulatory environment and excess advertisement of junk food – is a large part of the problem.22 23 24 But this data is compounded by other research, which shows that extended access to high-fat and high-sugar food, results in behavioral and physiological changes – which are similar to those caused by illegal drugs.25 [26] While a large portion of these corresponding studies were conducted on rats, this does not mean that the results will not translate to humans. Like many areas of scientific research, we simply need more data.

Baik JH. Dopamine signaling in food addiction: role of dopamine D2 receptors. BMB Rep. 2013;46(11):519-26.

As I’ve covered previously, the neurobiology of sugar addiction is fascinating as well.27 28 The brain is bombarded with an overwhelming amount of chemicals and reward, when you consume junk food.29 30 31 32 Over time, this leads to a higher quantity of junk food needing to be consumed, to achieve the same rewarding effect.33 34 35 So even for those of us who are not genetically susceptible to the temptations of junk food, we can alter our brain’s preferences and reward receptors, to become just as likely to crave it.36 37 38 39 40

Gómez-pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9(7):568-78.

The good side of all this bad news? Your brain can also be positively impacted by food.41 42 43 44 45 46 A Paleo diet, which is full of nutrient dense foods, will help keep you satiated, and keep your brain from craving high sugar, nutritionally empty choices. Be sure to load your plate with wild-caught fish (high in brain-friendly omega-3 fatty acids), healthy fats (like avocados) and complete sources of protein (like grass fed beef). You may indeed be hardwired for junk food – but that doesn’t mean you have to give in to temptation. Adopting a Paleo diet is associated with many different health benefits – many of which work to counteract the negative effects of junk food.47 48 49 50 What this means, is that you can improve your health drastically, by simply changing what’s on your plate. Start eating a Paleo diet today, and watch your health soar!

References

1. Available at: http://www.sciencedaily.com/releases/2015/11/151105103957.htm. Accessed November 23, 2015.

2. Available at: http://www.newswise.com/articles/are-you-hardwired-to-enjoy-high-calorie-foods-research-links-genes-to-heightened-brain-reward-responses-to-foods-high-in-fat-and-sugar. Accessed November 23, 2015.

3. Fortuna JL. The obesity epidemic and food addiction: clinical similarities to drug dependence. J Psychoactive Drugs. 2012;44(1):56-63.

4. Garber AK, Lustig RH. Is fast food addictive?. Curr Drug Abuse Rev. 2011;4(3):146-62.

5. Grimm O., Jacob M.J., Kroemer N.B., Krebs L., Vollstädt-Klein S., Kobiella A., Wolfensteller U., Smolka M.L. The personality trait self-directedness predicts the amygdala’s reaction to appetizing cues in fMRI. Appetite. 2012;58:1023–1029.

6. Macht M., Mueller J. Immediate effects of chocolate on experimentally induced mood states. Appetite.2007;49:667–674.

7. Kringelbach M.L. The human orbitofrontal cortex: Linking reward to hedonic experience. Nat. Rev. Neurosci. 2005;6:691–702.

8. Francis S.T., Head K., Morris P.G., Macdonald I.A. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J. Cardiovasc. Pharm. 2006;47:S215–S220.

9. Small D.M., Zatorre R.J., Dagher A., Evans A.C., Jones-Gotman M. Changes in brain activity related to eating chocolate: From pleasure to aversion. Brain. 2001;124:1720–1733.

10. Kemmotsu N., Murphy C. Restrained eaters show altered brain response to food odor. Physiol. Behav.2006;87:323–329.

11.  Blechert J., Feige B., Hajcak G., Tuschen-Caffier B. To eat or not to eat? Availability of food modulates the electrocortical response to food pictures in restrained eaters. Appetite. 2010;54:262–268.

12. Asmaro D, Liotti M. High-caloric and chocolate stimuli processing in healthy humans: an integration of functional imaging and electrophysiological findings. Nutrients. 2014;6(1):319-41.

13. Halpern CH, Tekriwal A, Santollo J, et al. Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation. J Neurosci. 2013;33(17):7122-9.

14. Lawrence NS, Hinton EC, Parkinson JA, Lawrence AD. Nucleus accumbens response to food cues predicts subsequent snack consumption in women and increased body mass index in those with reduced self-control. Neuroimage. 2012;63(1):415-22.

15. Salamone JD, Cousins MS, Mccullough LD, Carriero DL, Berkowitz RJ. Nucleus accumbens dopamine release increases during instrumental lever pressing for food but not free food consumption. Pharmacol Biochem Behav. 1994;49(1):25-31.

16. Olausson P, Jentsch JD, Tronson N, Neve RL, Nestler EJ, Taylor JR. DeltaFosB in the nucleus accumbens regulates food-reinforced instrumental behavior and motivation. J Neurosci. 2006;26(36):9196-204.

17. Day JJ, Carelli RM. The nucleus accumbens and Pavlovian reward learning. Neuroscientist. 2007;13(2):148-59.

18. Pratt WE, Kelley AE. Nucleus accumbens acetylcholine regulates appetitive learning and motivation for food via activation of muscarinic receptors. Behav Neurosci. 2004;118(4):730-9.

19. Salamone JD, Correa M, Mingote S, Weber SM. Nucleus accumbens dopamine and the regulation of effort in food-seeking behavior: implications for studies of natural motivation, psychiatry, and drug abuse. J Pharmacol Exp Ther. 2003;305(1):1-8.

20. Demos KE, Heatherton TF, Kelley WM. Individual differences in nucleus accumbens activity to food and sexual images predict weight gain and sexual behavior. J Neurosci. 2012;32(16):5549-52.

21. Available at: http://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Accessed November 23, 2015.

22. Yokum S, Gearhardt AN, Harris JL, Brownell KD, Stice E. Individual differences in striatum activity to food commercials predict weight gain in adolescents. Obesity (Silver Spring). 2014;22(12):2544-51.

23. Udo T, Weinberger AH, Grilo CM, et al. Heightened vagal activity during high-calorie food presentation in obese compared with non-obese individuals–results of a pilot study. Obes Res Clin Pract. 2014;8(3):e201-98.

24. Gearhardt AN, Roberto CA, Seamans MJ, Corbin WR, Brownell KD. Preliminary validation of the Yale Food Addiction Scale for children. Eat Behav. 2013;14(4):508-12.

25. Epstein DH, Shaham Y. Cheesecake-eating rats and the question of food addiction. Nat Neurosci. 2010;13(5):529-31.

26. Stockburger J., Schmälzle R., Flaisch T., Bublatzky F., Schupp H.T. The impact of hunger on food cue processing: An event-related brain potential study. Neuroimage. 2009;47:1819–1829.

27. Yang Q. Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. Yale J Biol Med. 2010;83(2):101-8.

28. García-cáceres C, Tschöp MH. The emerging neurobiology of calorie addiction. Elife. 2014;3:e01928.

29. Norton P, Falciglia G, Gist D. Physiologic control of food intake by neural and chemical mechanisms. J Am Diet Assoc. 1993;93(4):450-4.

30. Wurtman RJ. Nutrients affecting brain composition and behavior. Integr Psychiatry. 1987;5(4):226-38.

31. Young SN. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007;32(6):394-9.

32. Wang GJ, Volkow ND, Telang F, et al. Exposure to appetitive food stimuli markedly activates the human brain. Neuroimage. 2004;21(4):1790-7.

33. Baik JH. Dopamine signaling in food addiction: role of dopamine D2 receptors. BMB Rep. 2013;46(11):519-26.

34. Lietti C.V., Murray M.M., Hudry J., le Coutre J., Toepel U. The role of energetic value in dynamic brain response adaptation during repeated food image viewing. Appetite. 2012;58:11–18.

35. Meule A. Are certain foods addictive?. Front Psychiatry. 2014;5:38.

36. Davis C, Curtis C, Levitan RD, Carter JC, Kaplan AS, Kennedy JL. Evidence that ‘food addiction’ is a valid phenotype of obesity. Appetite. 2011;57(3):711-7.

37. Reward systems and food intake: role of opioids. International Journal of Obesity. 2009;:S54.

38. Naleid AM, Grace MK, Chimukangara M, Billington CJ, Levine AS. Paraventricular opioids alter intake of high-fat but not high-sucrose diet depending on diet preference in a binge model of feeding. Am J Physiol Regul Integr Comp Physiol. 2007;293(1):R99-105.

39. Woolley JD, Lee BS, Fields HL. Nucleus accumbens opioids regulate flavor-based preferences in food consumption. Neuroscience. 2006;143(1):309-17.

40. Zhang M, Gosnell BA, Kelley AE. Intake of high-fat food is selectively enhanced by mu opioid receptor stimulation within the nucleus accumbens. J Pharmacol Exp Ther. 1998;285(2):908-14.

41. Gómez-pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9(7):568-78.

42. Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006;10(5):377-85.

43. Hill JO, Berridge K, Avena NM, et al. Neurocognition: the food–brain connection. Adv Nutr. 2014;5(5):544-6.

44. Armelagos GJ. Brain evolution, the determinates of food choice, and the omnivore’s dilemma. Crit Rev Food Sci Nutr. 2014;54(10):1330-41.

45. Galland L. The gut microbiome and the brain. J Med Food. 2014;17(12):1261-72.

46. Lachance L, Ramsey D. Food, mood, and brain health: implications for the modern clinician. Mo Med. 2015;112(2):111-5.

47. Kowalski LM, Bujko J. Evaluation of biological and clinical potential of paleolithic diet.. Rocz Panstw Zakl Hig. 2012;63(1):9-15.

48. Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutr Clin Pract. 2010;25(6):594-602.

49. Klonoff DC. The beneficial effects of a Paleolithic diet on type 2 diabetes and other risk factors for cardiovascular disease. J Diabetes Sci Technol. 2009;3(6):1229-32.

50. Frassetto LA, Schloetter M, Mietus-synder M, Morris RC, Sebastian A. Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet. Eur J Clin Nutr. 2009;63(8):947-55.

This Is Your Brain on Paleo | The Paleo Diet
I’ve previously discussed the variety of positive neuronal changes that occur when consuming a healthier, Paleo Diet. This is especially true when you are moving away from a Western diet, filled with inflammatory seed oils, empty calories, and lots of sugar.1, 2 When consuming these foods, your brain literally reprograms itself, to come to crave and long after its next “fix.”3, 4 This is where changing your diet can not only help to change your body, but also your mind.5, 6

Take for example, the Nrf2 transcription factor. Nrf2 is a master regulator of intracellular redox homeostasis.7 Some research has shown that a ketogenic diet may activate the Nrf2 pathway via redox signaling, leading to chronic cellular adaptation, induction of protective proteins, and improvement of the mitochondrial redox state.8 Other research has shown that dietary flavonoids (mainly vegetables and fruits) are neuroprotective via proteins related to Nrf2.9 Nrf2, or nuclear factor erythroid 2-related factor 2, is critical for neuronal protection, through the induction of various cytoprotective genes.10

This Is Your Brain on Paleo | The Paleo Diet

McEwen, Bruce S. “Protective and Damaging Effects of Stress Mediators: Central Role of the Brain.” Dialogues in Clinical Neuroscience 8.4 (2006): 367–381. Print.

With this information in hand (or should I say, in your head) it starts to become clearer how making a simple change in your diet, can have many protective effects, especially when trying to avoid Alzheimer’s, or other debilitating neurological conditions.11 Many chronic diseases are underpinned by chronic inflammation, and yes, this extends to inflammation of the brain, as well.12, 13 As researchers have stated, the Keap1/Nrf2/ARE pathway plays a major role in health resilience and can be made more robust and responsive by certain dietary factors.14

With the damaging amount of free radicals produced by today’s high stress, low sleep and low nutrient lifestyles, it is time to take a serious look at just how much damage you are doing to your brain.15, 16 Do you think it is just a mere coincidence that the New England Journal of Medicine correlated higher average blood sugar (which occurs from consuming a high sugar diet) with an increased risk for dementia?17 I don’t. Our rates of crippling neurological disease have risen exponentially, as, simultaneously, has the rate of type 2 diabetes, which is obtained from, you guessed it, a high sugar diet.18

But it is not simply removing sugar that is the answer to all of our problems. It is also what foods and calories you are consuming, instead of the sugary breakfast cereals, pastries, and donuts. Vegetables have many beneficial compounds, which have been shown to help provide protection against neurological breakdown, and even enhance cell-to-cell signaling.19 This makes perfect sense given the many poor quality foods that can cause an increase in inflammatory chemical production.20 So, the basic hypothesis is simple: remove the foods causing the inflammation and higher rate of glycation (aging process), and replace them with foods that enhance neuronal signaling, and protect your brain from damage.21

This Is Your Brain on Paleo | The Paleo Diet
This Is Your Brain on Paleo | The Paleo Diet

“Result Filters.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 05 Jan. 2015.

One element not yet discussed, is BDNF, or brain-derived neurotrophic factor.22 A 2002 neuroscience study sums up this factor, and more specifically, how a poor diet can negatively affect your brain. Researchers concluded that a high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning.23 Unfortunately, the term “high fat,” continues to prevail in the scientific community, when researchers really mean trans fat, poor quality fat, and/or high fat plus high sugar. Nonetheless, this study easily conveys the idea that a poor diet will immediately cause problems in your hippocampus, your ability to learn, and how the brain reorganizes neuronal pathways in the brain. In a word: Bad.

This Is Your Brain on Paleo | The Paleo Diet

“Result Filters.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 05 Jan. 2015.

BDNF importance stems from not only helping to support the survival of existing neurons, but encouraging the growth of new neurons and synapses.24 Yes, this means that it, quite literally, can help you get smarter.25 So, if you’re consuming a poor diet, you will likely not be able to improve your intelligence at the same rate as you would, when consuming a healthier, Paleo Diet. BDNF is just one of the many factors that play into the neurological role of consuming healthy fats, high quality sources of protein and lots of vegetables, all key tenets of a Paleo Diet.

This Is Your Brain on Paleo | The Paleo Diet

“Result Filters.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 05 Jan. 2015.

Let’s talk about leptin resistance and what impact this condition has on your brain.26 When consuming a poor diet, you are very likely to develop insulin resistance.27 Accompanying that, is usually leptin resistance.28 Leptin is your body’s way of telling your brain that you are full, and you do not need to eat any more food.29 Those born with a leptin deficiency, almost immediately become obese, because their brain simply cannot realize they have consumed enough calories.30

But leptin resistance, rather than leptin deficiency, means you are now resistant to the body’s way of telling your brain to stop eating.31 This leads to a whole host of problems, the least of which, is over consumption and the resulting weight gain.32 Researchers have found that chronically elevated leptin decreases hypothalamic leptin receptor expression and protein levels and impairs leptin signaling.33 This is only the first step in the vicious cycle of weight gain via leptin resistance.34 Since hypothalamic leptin receptor expression has been decreased, your brain actually changes from consuming a poor diet.35, 36, 37

Many people are unaware of all the pathways and details that come from simply changing the food that is on their plate. But the many crucial scientific changes that occur, silently, but steadily, are what really lead to obesity and disease.38, 39 Becoming aware of them, and changing what you put in your mouth, is perhaps the single most important thing you can do, to get healthier and to save yourself from a lifetime of chronic disease and unhappiness.40, 41 A Paleo Diet is brain-friendly, and will be one of the biggest changes you make, to become smarter, happier, leaner, and disease-free!

REFERENCES

[1] Gutiérrez-fisac JL, Angel royo-bordonada M, Rodríguez-artalejo F. [Health-risks associated with Western diet and sedentariness: the obesity epidemia]. Gac Sanit. 2006;20 Suppl 1:48-54.

[2] Poti JM, Duffey KJ, Popkin BM. The association of fast food consumption with poor dietary outcomes and obesity among children: is it the fast food or the remainder of the diet?. Am J Clin Nutr. 2014;99(1):162-71.

[3] Heatherton TF. Neuroscience of self and self-regulation. Annu Rev Psychol. 2011;62:363-90.

[4] Berthoud HR. The neurobiology of food intake in an obesogenic environment. Proc Nutr Soc. 2012;71(4):478-87.

[5] Pilot randomized trial demonstrating reversal of obesity-related abnormalities in reward system responsivity to food cues with a behavioral intervention. Nutrition & Diabetes. 2014;4(9):e129.

[6] Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/news/2014-09-02-brain-can-be-retrained-to-prefer-healthy-foods/. Accessed December 30, 2014.

[7] Zhang YK, Wu KC, Liu J, Klaassen CD. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. Toxicol Appl Pharmacol. 2012;264(3):305-14.

[8] Milder JB, Liang LP, Patel M. Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet. Neurobiol Dis. 2010;40(1):238-44.

[9] Leonardo CC, Doré S. Dietary flavonoids are neuroprotective through Nrf2-coordinated induction of endogenous cytoprotective proteins. Nutr Neurosci. 2011;14(5):226-36.

[10] Available at: http://www.ncbi.nlm.nih.gov/gene/4780. Accessed December 28, 2014.

[11] Ravona-springer R, Moshier E, Schmeidler J, et al. Changes in glycemic control are associated with changes in cognition in non-diabetic elderly. J Alzheimers Dis. 2012;30(2):299-309.

[12] Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun. 2004;18(5):407-13.

[13] Calderón-garcidueñas L, Reed W, Maronpot RR, et al. Brain inflammation and Alzheimer’s-like pathology in individuals exposed to severe air pollution. Toxicol Pathol. 2004;32(6):650-8.

[14] Stefanson AL, Bakovic M. Dietary regulation of Keap1/Nrf2/ARE pathway: focus on plant-derived compounds and trace minerals. Nutrients. 2014;6(9):3777-801.

[15] Mcewen BS. Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci. 2006;8(4):367-81.

[16] Cohen JI, Yates KF, Duong M, Convit A. Obesity, orbitofrontal structure and function are associated with food choice: a cross-sectional study. BMJ Open. 2011;1(2):e000175.

[17] Crane PK, Walker R, Hubbard RA, et al. Glucose levels and risk of dementia. N Engl J Med. 2013;369(6):540-8.

[18] Moreira PI. High-sugar diets, type 2 diabetes and Alzheimer’s disease. Curr Opin Clin Nutr Metab Care. 2013;16(4):440-5.

[19] Choi HS, Jeon HJ, Lee OH, Lee BY. Indole-3-carbinol, a vegetable phytochemical, inhibits adipogenesis by regulating cell cycle and AMPKα signaling. Biochimie. 2014;104:127-36.

[20] Mattson MP, Chan SL, Duan W. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev. 2002;82(3):637-72.

[21] Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014;6(9):707-17.

[22] Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22(3):123-31.

[23] Molteni R, Barnard RJ, Ying Z, Roberts CK, Gómez-pinilla F. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience. 2002;112(4):803-14.

[24] Song C, Fang S, Lv G, Mei X. Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord. Neural Regen Res. 2013;8(15):1383-9.

[25] Rostami E, Krueger F, Zoubak S, et al. BDNF polymorphism predicts general intelligence after penetrating traumatic brain injury. PLoS ONE. 2011;6(11):e27389.

[26] Eikelis N, Wiesner G, Lambert G, Esler M. Brain leptin resistance in human obesity revisited. Regul Pept. 2007;139(1-3):45-51.

[27] Johnson-down L, Labonte ME, Martin ID, et al. Quality of diet is associated with insulin resistance in the Cree (Eeyouch) indigenous population of northern Québec. Nutr Metab Cardiovasc Dis. 2014;

[28] Lustig RH, Sen S, Soberman JE, Velasquez-mieyer PA. Obesity, leptin resistance, and the effects of insulin reduction. Int J Obes Relat Metab Disord. 2004;28(10):1344-8.

[29] Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007;8(1):21-34.

[30] Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903-8.

[31] Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol. 2008;70:537-56.

[32] Martin SS, Qasim A, Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol. 2008;52(15):1201-10.

[33] Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763.

[34] Vasselli JR. The role of dietary components in leptin resistance. Adv Nutr. 2012;3(5):736-8.

[35] Mitchell SE, Nogueiras R, Morris A, et al. Leptin receptor gene expression and number in the brain are regulated by leptin level and nutritional status. J Physiol (Lond). 2009;587(Pt 14):3573-85.

[36] Gamber KM, Huo L, Ha S, Hairston JE, Greeley S, Bjørbæk C. Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. PLoS ONE. 2012;7(1):e30485.

[37] Korner J, Savontaus E, Chua SC, Leibel RL, Wardlaw SL. Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. J Neuroendocrinol. 2001;13(11):959-66.

[38] Chakraborty S, Zawieja S, Wang W, Zawieja DC, Muthuchamy M. Lymphatic system: a vital link between metabolic syndrome and inflammation. Ann N Y Acad Sci. 2010;1207 Suppl 1:E94-102.

[39] Kolčić I. Double burden of malnutrition: A silent driver of double burden of disease in low- and middle-income countries. J Glob Health. 2012;2(2):020303.

[40] Frassetto LA, Schloetter M, Mietus-synder M, Morris RC, Sebastian A. Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet. Eur J Clin Nutr. 2009;63(8):947-55.

[41] Fujimura KE, Slusher NA, Cabana MD, Lynch SV. Role of the gut microbiota in defining human health. Expert Rev Anti Infect Ther. 2010;8(4):435-54.

Gluten & the Brain | The Paleo Diet

With the plethora of benefits supported by scientific evidence,1 Gluten-free diets have been gaining in popularity in recent years.2 Studies range from gastrointestinal symptom improvement,3 to possible correlations with autism,4 and diabetes.5 However, there may not be a more fascinating area of gluten study than how the protein composite can be related to cognitive function.6 One study shows large changes in brain tissue, specifically, white matter, in those who are sensitive to gluten.7

Gluten MRI

Gluten and White Matter in the Brain

Why is this an important discovery? White matter is actively involved in neurogenesis, or “the growth of new neurons.”8, 9, 10 If gluten is possibly disrupting this process, like chemotherapy has been studied to do,11 then its effects may not be just temporary and transient. Instead they may be both long lasting and potentially damaging.12

Stress, sleep disruption, exercise and inflammation have all been linked with regulating hippocampal neurogenesis and implicated in the pathophysiology of mood disorders.13 But can gluten be linked to mood disorders? The science says yes.14

Many reports evidence unexpected resolution of long-term schizophrenic symptoms, when eliminating gluten from the diet.15 Interestingly, one study of Pacific Islanders who consumed almost no grains (or dairy) showed that only 2 in 65,000 subjects presented with overtly psychotic cases of schizophrenia.16, 17 However, since there are oftentimes confounding variables in these studies, it is not yet mechanistically clear on what may be causing remission of symptoms.18

In regards to cognitive function, as far back as 2004, scientists have shown improvements in the frontal region of the brain, in subjects consuming a gluten-free diet.19 Other research shows gluten’s effects are clearly not limited to gastrointestinal issues alone.20

Mapping of α-gliadin motifs

 

Gluten-Related Algorithm

Proposed algorithm for the differential diagnosis of gluten-related disorders, including celiac disease, gluten sensitivity and wheat allergy.

To whom does this apply21 and how exactly does gluten cause cognitive impairment? Definitively, we can seem to say that removing gluten from the diet improves cognitive functioning in many individuals.22, 23 Gluten elicits an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 genes.24

The “foggy brain” symptoms, as reported by non-celiac disease subjects, are intriguing. In these subjects, we see an up-regulation of claudin-4, which is associated with an increased expression of toll-like receptor-2 and a significant reduction of the T-regulatory cell marker FoxP3.25 This is part of why an innate immune system response seems to be involved in these subjects, rather than an adaptive immune system response.

Gluten sensitivity as a neurological illness

However, individuals diagnosed with celiac disease, α-amylase/trypsin inhibitors (ATIs) are strong activators of innate immune system responses in macrophages, monocytes and dendritic cells, via toll-like receptor-4.26 Despite these details, however, we cannot yet definitively say that gluten causes cognitive impairment,27, 28 no matter how likely it may seem in the scientific literature.

Brain MRI: Gluten Ataxia

Brain MRI of a patient with gluten ataxia showing rapid onset of cerebellar atrophy over a period of 15 months before the diagnosis of gluten ataxia.

The distinction is very important. A much-publicized study29 from early 2014 suggested it might not be gluten itself that causes issues, but instead it may agglutinins, FODMAPs, prodynorphins, deamidated gliadin and/or gliadorphins.

These findings illustrate more studies need to be done in order to show, mechanistically, what is causing physiologic disruptions, changes in white matter. Furthermore, research may determine distinct populations that should avoid gluten, if indeed the protein composite is causing these issues.

“Early diagnosis and removal of the trigger factor, by the introduction of a gluten-free diet, is a promising therapeutic intervention,” said researchers in a study published in the Journal of Neurology.30 A promising intervention – that needs much more research.31

I do not dismiss anecdotal improvements seen in individuals adopting gluten-free diets, such as the Paleo Diet. And with that said, we need instead maintain scientific rigor and provide the best, most accurate, recommendations possible.

The negative effects of gluten and other gluten-like compounds have been well-documented for many years.32, 33, 34, 35 Just because a specific mechanism for neurologic dysfunction hasn’t yet been identified – doesn’t mean gluten is doing anyone any favors.36, 37

We must also remember that although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors.38, 39 A Paleo Diet still provides the best defense against neurologic impairment, as well as providing favorable changes in risk factors, such as weight, waist circumference, C-reactive protein, glycated haemoglobin (HbAlc), blood pressure, glucose tolerance, insulin secretion, insulin sensitivity and lipid profiles.40



References

1. Soares FL, De oliveira matoso R, Teixeira LG, et al. Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression. J Nutr Biochem. 2013;24(6):1105-11.

2. Available at: http://www.cbsnews.com/news/gluten-free-diet-more-popular-than-ever-but-who-really-needs-it/. Accessed August 3, 2014.

3. Murray JA, Watson T, Clearman B, Mitros F. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr. 2004;79(4):669-73.

4. Buie T. The relationship of autism and gluten. Clin Ther. 2013;35(5):578-83.

5. Sildorf SM, Fredheim S, Svensson J, Buschard K. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Rep. 2012;2012

6. Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA. Cognitive impairment and celiac disease. Arch Neurol. 2006;63(10):1440-6.

7. Hadjivassiliou M, Grünewald RA, Lawden M, Davies-jones GA, Powell T, Smith CM. Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology. 2001;56(3):385-8.

8. Liu XS, Chopp M, Kassis H, et al. Valproic acid increases white matter repair and neurogenesis after stroke. Neuroscience. 2012;220:313-21.

9. Takemura NU. Evidence for neurogenesis within the white matter beneath the temporal neocortex of the adult rat brain. Neuroscience. 2005;134(1):121-32.

10. Gould E, Reeves AJ, Graziano MS, Gross CG. Neurogenesis in the neocortex of adult primates. Science. 1999;286(5439):548-52.

11. Nokia MS, Anderson ML, Shors TJ. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain. Eur J Neurosci. 2012;36(11):3521-30.

12. Lichtwark IT, Newnham ED, Robinson SR, et al. Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity. Aliment Pharmacol Ther. 2014;40(2):160-70.

13. Lucassen PJ, Meerlo P, Naylor AS, et al. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur Neuropsychopharmacol. 2010;20(1):1-17.

14. Dickerson F, Stallings C, Origoni A, et al. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disord. 2011;13(1):52-8.

15. Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond). 2009;6:10.

16. Dohan FC, Harper EH, Clark MH, Rodrigue RB, Zigas V. Is schizophrenia rare if grain is rare?. Biol Psychiatry. 1984;19(3):385-99.

17. Dohan FC. Genetic hypothesis of idiopathic schizophrenia: its exorphin connection. Schizophr Bull. 1988;14(4):489-94.

18. Di sabatino A, Corazza GR. Nonceliac gluten sensitivity: sense or sensibility?. Ann Intern Med. 2012;156(4):309-11.

19. Usai P, Serra A, Marini B, et al. Frontal cortical perfusion abnormalities related to gluten intake and associated autoimmune disease in adult coeliac disease: 99mTc-ECD brain SPECT study. Dig Liver Dis. 2004;36(8):513-8.

20. Hadjivassiliou M, Grünewald RA, Davies-jones GA. Gluten sensitivity: a many headed hydra. BMJ. 1999;318(7200):1710-1.

21. Troncone R, Jabri B. Coeliac disease and gluten sensitivity. J Intern Med. 2011;269(6):582-90.

22. Genuis SJ, Lobo RA. Gluten sensitivity presenting as a neuropsychiatric disorder. Gastroenterol Res Pract. 2014;2014:293206.

23. Bürk K, Bösch S, Müller CA, et al. Sporadic cerebellar ataxia associated with gluten sensitivity. Brain. 2001;124(Pt 5):1013-9.

24. Junker Y, Zeissig S, Kim SJ, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012;209(13):2395-408.

25. Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012;10:13.

26. Laparra, M., Zevallos, V. and Schuppan, D. (n.d.). Influence of faecal contents from a gluten-free vs. gluten-containing diet on alpha-amylase/trypsin inhibitor-mediated inflammation. Zeitschrift fur Gastroenterologie, 50(08), p.174.

27 Poloni N, Vender S, Bolla E, Bortolaso P, Costantini C, Callegari C. Gluten encephalopathy with psychiatric onset: case report. Clin Pract Epidemiol Ment Health. 2009;5:16.

28 Gluten sensitivity as a neurological illness. Journal of Neurology, Neurosurgery & Psychiatry. 2002;72(5):560.

29. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology. 2013;145(2):320-8.e1-3.

30. Gluten sensitivity as a neurological illness. Journal of Neurology, Neurosurgery & Psychiatry. 2002;72(5):560.

31. Biesiekierski JR, Muir JG, Gibson PR. Is gluten a cause of gastrointestinal symptoms in people without celiac disease?. Curr Allergy Asthma Rep. 2013;13(6):631-8.

32. Norström F, Sandström O, Lindholm L, Ivarsson A. A gluten-free diet effectively reduces symptoms and health care consumption in a Swedish celiac disease population. BMC Gastroenterol. 2012;12:125.

33. Gasbarrini G, Mangiola F. Wheat-related disorders: A broad spectrum of ‘evolving’ diseases. United European Gastroenterol J. 2014;2(4):254-62.

34. Paoloni M, Tavernese E, Ioppolo F, Fini M, Santilli V. Complete remission of plantar fasciitis with a gluten-free diet: Relationship or just coincidence?. Foot (Edinb). 2014;

35. Cordain L. Cereal grains: humanity’s double-edged sword. World Rev Nutr Diet. 1999;84:19-73.

36. Lachance LR, Mckenzie K. Biomarkers of gluten sensitivity in patients with non-affective psychosis: a meta-analysis. Schizophr Res. 2014;152(2-3):521-7.

37. Catassi C, Bai JC, Bonaz B, et al. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013;5(10):3839-53.

38. O’keefe JH, Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clin Proc. 2004;79(1):101-8.

39. Cordain L, Eaton SB, Sebastian A, et al. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005;81(2):341-54.

40. Kowalski LM, Bujko J. [Evaluation of biological and clinical potential of paleolithic diet]. Rocz Panstw Zakl Hig. 2012;63(1):9-15.

Grain Brain

Hi Loren,

I was hoping I could induce you to correct a statement made about your work in a recent post in The Atlantic. It’s by a senior editor, a medical doctor, James Hamblin, who’s doing a take-down of Perlmutter’s Grain Brain couched as a piece of journalism. In it he quotes David Katz of Yale, commenting about the paleolithic diet and your work.

I thought perhaps you could take a little time to set both Hamblin and maybe even Katz right. The key section:

“Of course,” Katz added, “Everything about the Paleolithic Era is subject to debate. Most of us don’t know what we had for breakfast yesterday, let alone what people were doing 100,000 years ago. Yeah, I’ve read the same thing that the average life expectancy was between 20 and 40 and, consequently, the diseases of old age didn’t happen because old age didn’t happen. There’s nothing about their diet that we know to be protective against things like Alzheimer’s. That’s just silly.”

Perlmutter has estimated that the Stone Age diet was 75 percent fat, a claim Katz finds “wildly preposterous.” Anthropological research, he pointed out the work of Loren Cordain, suggests that in the age before cooking oil, humans ate mostly plants with a scattering of seeds and nuts. “Virtually nothing in the natural world is that concentrated of a fat source, except maybe for the brain. Maybe if they just ate the brains of animals? They didn’t have oil. They only started adding oil to the diet after the Dawn of Agriculture. What the hell could they possibly have eaten that would be that fatty?'”

This kind of journalism is bad enough when they get the facts vaguely right and just spin them to fit their biases. When they butcher the facts, too, it deserves correcting.

All the best,

Gary Taubes

Gary Taubes is the author of Why We Get Fat (2011), Nobel Dreams (1987), Bad Science: The Short Life and Weird Times of Cold Fusion (1993), and Good Calories, Bad Calories (2007), which is titled The Diet Delusion in the UK. He has won the Science in Society Award of the National Association of Science Writers three times and was awarded an MIT Knight Science Journalism Fellowship. Taubes studied applied physics at Harvard and aerospace engineering at Stanford (MS, 1978). Taubes has written numerous articles for Discover, Science and other magazines. Originally focusing on physics issues, his interests have more recently turned to medicine and nutrition.

Dr. Cordain’s Response:

Hi Gary,

Good to hear from you.  Thanks for forwarding me the article from The Atlantic by James Hamblin, MD. on Perlmutter’s Grain Brain. I came away with a number of impressions:

1.  Both Katz and Perlmutter acknowledge the underlying, evolutionary basis for human nutrition.

2.  Scientists involved in gluten research and Paleo Diets (including myself) were not directly interviewed in this article.  This omission likely fuels Hamblin’s perspective and does not provide equal input for both sides of the argument.

3.  I was not interviewed for this article and the quote you cite below is not mine, but rather appears to be David Katz’s interpretation of our work.  The quote is erroneous as well as being just flat out wrong.  Our group has repeatedly analyzed the composition and macronutrient content of historically studied hunter gatherer diets.1-7 Animal fat has been an integral part of hominid diets since the origins of our genus Homo.  To correct whomever wrote the erroneous quote below, regardless of whether fat comes from either plant or animal food sources, it contains identical caloric densities (9 kcal/g).  In the typical hunter gatherer diet, animal fat would have generally exceeded plant fat on an average daily basis.

Brain contains virtually no fat, but rather is comprised primarily of fatty acids bound to the phospholipid fraction.  A fat (triglyceride) is also technically called an acylglycerol (a glycerol molecule bound to a fatty acid [acyl group] via an ester bond).   Brain contains little or no acylglycerol, but rather structural fatty acids found not in the triglyceride fraction, but in the phospholipids fraction.   There is no doubt that brain, marrow and other fatty (and fatty acid) portions of wild animal carcasses would have been preferred by our hunter gatherer ancestors over lean meats.

Cordially,

Loren Cordain, Ph.D., Professor

 

REFERENCES

1. Cordain L, Brand Miller J, Eaton SB, Mann N, Holt SHA, Speth JD. Plant to animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. American Journal of Clinical Nutrition, 2000, 71:682-92.

2. Cordain L, Eaton SB, Brand Miller J, Mann N, Hill K. The paradoxical nature of hunter-gatherer diets: Meat based, yet non-atherogenic. Eur J Clin Nutr 2002;56 (suppl 1):S42-S52.

3. Cordain L, The nutritional characteristics of a contemporary diet based upon Paleolithic food groups. J Am Neutraceut Assoc 2002; 5:15-24.

4. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the western diet: Health implications for the 21st century. Am J Clin Nutr 2005;81:341-54.

5. Cordain L. Saturated fat consumption in ancestral human diets: implications for contemporary intakes. In: Phytochemicals, Nutrient-Gene Interactions, Meskin MS, Bidlack WR, Randolph RK (Eds.), CRC Press (Taylor & Francis Group), 2006, pp. 115-126.

6. Ramsden CE, Faurot KR, Carrera-Bastos P, Sperling LS, de Lorgeril M, Cordain L. Dietary fat quality and coronary heart disease prevention: a unified theory based on evolutionary, historical, global and modern perspectives. Curr Treat Options Cardiovasc Med; 2009;11:289-301.

7. Kuipers RS, Luxwolda MF, Janneke Dijck-Brouwer DA, Eaton SB, Crawford MA, Cordain L, Muskiet FA. Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. Brit J Nutr , 2010 Dec;104(11):1666-87.

Sign up for Email Newsletters!

We guarantee 100% privacy.
Your information will not be shared.

×