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Navigating the Convoluted Road to and from Depression

by Nora T. Gedgaudas, CNS, CNT, BCHN

A Growing Epidemic

Major depression, the most common form of mental illness, is by some expected to be the second leading cause of disability by 2020 worldwide – second only to ischemic heart disease, according to the CDC.1The World Health Organization projected that depression may become the biggest health burden in the world within a mere 20 years (as of 2001).2 Much more than being a simple “emotional disorder,” persons with major depression (along with schizophrenia) commonly experience disproportionately higher rates of disability and mortality. There is literally a 40% to 60% greater chance among such persons of dying prematurely than in the general population.3 Women seem to be at greatest risk.

In short, the prognosis for mental health of the population isn’t a good one. In the US alone, the lifetime risk for major depression is already just over a quarter of the population (26%).4 It is a debilitating condition characterized by prolonged feelings of sadness, loss of interest in activities, and decreased energy. Other symptoms include loss of confidence and self-esteem, inappropriate guilt, thoughts of death and suicide, diminished concentration, and disturbance of sleep and appetite. A variety of somatic symptoms may also be present. Though short-term forms of depression and anxiety may be natural adaptive responses to emotional stressors and setbacks in our lives, what is officially termed depressive disorder is typically diagnosed when the symptoms reach a certain threshold and last at least 2 weeks.

Perhaps the greatest myth among those who have not experienced significant depression is the idea that depression is somehow a “passive” condition, characterized by a “failure” of appropriate habits such as exercise and positive thinking. In fact, depression is truly a state of “chronic efforting” wherein its sufferers are continually spinning their wheels on the edge of an icy road, exhausting themselves without being able to go anywhere; trapped in a perpetual state of helplessness and hopelessness. In my experience, most depression appears to additionally lie on the flipside of a coin paired with anxiety, ultimately constituting a state of what could be termed “anxiety to exhaustion.”

A Premise

We all see the world through a lens that is our biochemistry: our hormones, our neurotransmitters, and (the degree to which we choose to depend on it) our blood sugar. These factors are inherent to our interpretation of the world around us. I would propose that all of these factors are additionally interrelated, and that from a foundational perspective, we largely generate the focus our own internal lens by what we choose to eat.

Every single physiological process and biochemical reaction in the human body is wholly dependent upon the nutrients in our diets and other (perhaps less than nutritive) compromising substances that we supply these processes with. Genes are almost wholly controlled by epigenetic factors (i.e., dietary and other environmental influences). Therefore, our underlying mental state is very powerfully influenced by what we feed it (on multiple levels) – or don’t.5^,6

The fact is that understanding the foundational requirements behind our unique human design and where things might be lacking is essential to virtually anyone’s restoration of function.

So where do we start?

Going Back to Our Humble Evolutionary Beginnings

It makes practical sense to take our long evolutionary history into account when it comes to thisequation. The premise is this: those foods that we would have habitually consumed as a species for the longest period of time would constitute our greatest genetic and dietary adaptations and would be most foundational to our underlying physiological makeup and nutritional requirements. To me this consideration is an essential starting place.

As the wild hominids that we once were, resources and food availability would have been variably limited; therefore quality nutrient density would have been of paramount importance and highly coveted. As understood by most paleoanthropologists today, it was likely our dependence on the meat and especially fat of the animals which we hunted that not only allowed us to survive but also consequently resulted in the very rapid enlargement of the human brain.7

Primal Fat-Heads

On average, humans are designed to and also tend to consume significantly higher levels of dietary fat than other primates.8 We also evolved consuming much higher levels of particularly key long-chain polyunsaturated fatty acids (LC-PUFAs) that are critical to brain development that we got directly from the wild (grass-fed) meat, organs, and tissues of the animals we hunted.9^,10 Human brain growth and function are in fact primarily dependent on dietary fats (particularly 20 and 22 carbon fatty acids, DHA, and AA) – in other words, dietary animal source fats.11

Curse of the ‘Sugar-Burning Blues’

The mantra of mainstream medicine and conventional dieticians/nutritionists commonly taught and blindly accepted as an “absolute truth” is that glucose is required by all tissues, including the brain, for everyday energy. This is misleading and only conditionally true; it is only true if we have metabolically adapted ourselves to the unnatural dependence on glucose as our primary source of fuel by the excessive and chronic consumption of sugar and starch (a hallmark of the Western diet and even of USDA dietary recommendations). Glucose as a primary source of metabolic fuel is a volatile, inefficient and unreliable source of prolonged energy and requires frequent replenishment as well as constant management for its stability. But, luckily, Mother Nature was not so stupid as to force a dependence upon a single fuel – and certainly not one as fickle as blood sugar. The inflammatory tidal waves of insulin generated in the name of blood sugar management as a result of the modern standard American diet are something that would have been largely foreign to our ancient ancestral forebears. The emergency physiological need to “lower blood sugar” (via chronic insulin demand) is a strictly modern phenomenon to which we as human beings are ill suited. A significant percentage of physical, cognitive, and mental health-related problems can potentially be traced to this modern-day, perpetually abnormal metabolic state, which I discuss in much more depth and detail in my book, Primal Body, Primal Mind: Beyond the Paleo Diet for Total Health and a Longer Life.12

Life in the “level zone” (depicted above) becomes more constant on a ketogenic diet and blood sugar influence upon mood and energy becomes effectively irrelevant.

Source: Nora T. Gedgaudas by permission

The human brain is fortuitously designed to make use of more than just one primary form of fuel, however. It is in fact ketones (i.e., the energy units of fat), and not blood sugar (glucose) that can most readily provide our metabolically expensive brain’s absolute best and most efficient form of long burning, sustainable energy.

Sugar and Starch As Prime Fodder for Mood-related Issues and Neurological Instability

The presence of significantly elevated blood sugar has the effect of initially increasing L-tryptophan levels in the bloodstream (called the plasma-tryptophan ratio) that may then (assuming the availability of necessary cofactors) technically be diverted to serotonin production. In the short term, this undoubtedly feels good and may have a brief mood-enhancing effect. Long term, however, sugar- and starch-based foods lack sufficient raw materials necessary in their composition (i.e., amino acids and/or B-vitamins required to supply more L-tryptophan and/or manufacture serotonin). As such, the effect over time is ultimately more depleting than anything. Tryptophan is the least abundant amino acid in our food supply and is particularly lacking in grain-based diets. Sugar additionally lights up opiate centers in the brain, which triggers its own desire for more. The potential for addiction and a downward spiral in mood is ever present and in certain sensitive individuals may lead to other carbohydrate-related/blood-sugar dysregulation issues such as metabolic diseases and alcoholism. The short-term sugar high rarely leads to any form of long-term health or happiness.

One 2013 study of more than 23,000 mothers and their children suggested a link between a mother’s consumption of sweets and processed foods during pregnancy and behavioral and mental health issues in her child at age 5. The results stated, “Higher intakes of unhealthy foods during pregnancy predicted externalizing problems among children, independently of other potential confounding factors and childhood diet. Children with a high level of unhealthful diet postnatally had higher levels of both internalizing and externalizing problems. Moreover, children with a low level of postnatal healthy diet also had higher levels of both internalizing and externalizing problems.” The authors concluded, “Early nutritional exposures were independently related to the risk for behavioral and emotional problems in children.”13

Hypoglycemia and reactive hypoglycemia are relatively common in the population today, and especially among those with mood lability, irritable tendencies, depression, and anxiety-related issues. As such, many individuals deal quite poorly with our government-sanctioned standard carbohydrate-based diet. In fact, there is nothing more destabilizing to the brain and nervous system than a diet fundamentally based on sugar and starch – especially refinedcarbohydrates.

The Better Alternative

Cultivating more of a natural, ancestrally aligned, fat-based, ketogenic metabolism (typically requiring an intake of no more than about 50 g/day of utilizable sugar/starch) may be the single most effective means of both optimally feeding and stabilizing any brain or nervous system. In this particular ketogenic approach (as there are many), grass-fed meat and accompanying fats, uncontaminated and wild-caught fish/seafood dairy, nuts, olive oil, and avocado – together with unlimited amounts of organic, nonstarchy fibrous vegetables and greens are top of the list in terms of foods that comply.

A similar dietary approach has shown efficacy in at least one study related to bipolar II disorder. In the 2013 peer reviewed study the authors stated,

Two women with type II bipolar disorder were able to maintain ketosis for prolonged periods of time (2 and 3 years, respectively). Both experienced mood stabilization that exceeded that achieved with medication; experienced a significant subjective improvement that was distinctly related to ketosis; and tolerated the diet well. There were no significant adverse effects in either case. These cases demonstrate that the ketogenic diet is a potentially sustainable option for mood stabilization in type II bipolar illness. They also support the hypothesis that acidic plasma may stabilize mood, perhaps by reducing intracellular sodium and calcium.14 (emphasis mine)

Not only this, according to an article published in the American Journal of Physiology in 1996, “A ketogenic state results in a substantial (39%) increase in cerebral blood flow, and appears to reduce cognitive dysfunction associated with systemic hypoglycemia in normal humans.”15 (emphasis mine). Seeing as cerebral hypoperfusion to the frontal cortex is one typical hallmark associated with depressive symptoms, improving brain circulation by a whopping 39% is potentially highly significant!

Researchers observing the comparative impact to a glucose vs. ketone-based metabolism in a study published in the Neurobiology of Aging had the following observation:

As compared with glucose metabolism, central ketone metabolism generates lower levels of oxidative stress (Prins, 2008) and has been shown to produce greater cellular energy output and antioxidant capacity, the latter by increasing glutathione peroxidase in hippocampal cells (Veech et al., 2001; Ziegler et al.. 2003). In addition, the presence of cerebral ketones is associated with decreased apoptosis and inflammation (Gasior et al., 2006; Malouf et al., 2009), which along with oxidative stress, have been identified as fundamental factors contributing to neurodegeneration (Cotman, 2000).16

The anti-inflammatory effects of a state of ketosis here (along with the pro-inflammatory effects of increased blood sugar) are especially pertinent to this discussion, as the neurotransmitter deficiency model and theory of depression is currently being replaced by independent researchers by something now referred to as “the cytokine model of depression.”17 In other words, today depression is being increasingly understood by researchers as an inflammatory disorder rather than any sort of foundational “neurotransmitter deficiency.” Naturally, the old, largely ineffective pharmacologic SSRI model, still profitable enough, persists in spite of this.

One more highly inconvenient truth: Sugar is far from the only culprit when it comes to the impact of postagricultural foods on the dysregulation and deleterious impacts on the human brain. Welcome to the post-wooly mammoth agricultural age. …

The Gluten–Mental Health Connection

Source: By permission from Nora T. Gedgaudas

A review paper published in the New England Journal of Medicine dating all the way back to 2002 listed 55 conditions that were found to be associated with eating gluten.18 Today this number potentially exceeds 200 and includes virtually all forms of autoimmune disease, currently numbering close to 100, with 40 additional diseases that are thought to have an autoimmune component.19 According to the American Autoimmune Related Diseases Association, as many as 53 million Americans currently suffer from some form of autoimmune disease, as compared with cancer, currently thought to be affecting 9 million Americans, and cardiovascular disease, currently thought to be affecting 22 million Americans: autoimmunity appears to be exceeding both of these combined. Gluten, an indigestible protein found in wheat, barley, and rye, is nearly ubiquitous in processed foods and personal-care products. It is known to potentially initiate or exacerbate essentially all autoimmune processes, and its consumption poses a very high risk factor. The presence of almost any type of symptom should motivate anyone to immediately rule out gluten immune reactivity through accurate (i.e., Cyrex Labs) testing. Among these conditions, numerous psychiatric disorders and cognitive issues that one might not necessarily think of as being associated with autoimmunity can be potentially included here.20^–24

• An estimated 54.1% of people with depression may have autoimmunity against their own serotonin receptors.25^–27
• More than 80% and quite possibly more than 90% of all low-functioning thyroid cases (in many cases presenting with depressive symptoms) are actually autoimmune in nature.28
• Bipolar–disorder type symptoms are found to be highly correlated with thyroid autoimmunity.29^–31

As I pointed out in my book, “Depression has been found in 67% of patients with untreated celiac disease.”32 The same study found that high levels of anxiety are also exceedingly common in such patients (73%). Gluten sensitivity (or the possibility of it) cannot be ignored here as a contributing factor or underlying culprit. In an article in Alimentary Pharmacology & Therapeutics,the author stated, “Depression is reported to be a feature of celiac disease and is ranked as its most common neuropsychiatric disturbance.”33 Food sensitivities in general always need to be considered wherever depression or anxiety is an issue.

Tending to Your Internal Wildlife and the Brain–Gut Superhighway

Among the biggest buzzwords heard in the natural health field today is microbiome. Indeed, as 90% of the cells making up the human body are bacterial, fully 99% of the genetic material occupying the human organism at large is fundamentally “alien” (i.e., nonhuman) in nature. These microscopic hoards occupy every nook and cranny of our second brain (i.e., the GI tract) in varying concentrations and types, as well as elsewhere within the human body, be they welcome or not. Without question these vast populations of living organisms within our own have their own agenda, requirements, and varied physiological impact that must be seriously taken into account. The relative health or pathology of these populations has demonstrably pronounced consequences upon our own.

Gut bacteria (over 1000 different species numbering up to 100 trillion) are being discovered increasingly to have a major influential role in brain health and functioning, as well as mood. Gut bacteria both produce and respond to the same neurochemicals – such as GABA, serotonin, norepinephrine, dopamine, acetylcholine, and melatonin – that the brain uses to regulate its moods and cognition. In part, these neurochemicals may align the brain and its behavior to the feedback that it receives from the bacteria living in the gut. Obviously, cultivating and maintaining healthy probiotic colonization of the gut should certainly be a priority with any brain-related issue.

Currently, psychiatric disorders thus far connected with the health of the microbiota include anxiety, depression, autism/ASD, Alzheimer’s disease, schizophrenia, and eating disorders, to name a few. The presence or absence of various microorganisms within the gut seems to be able to even powerfully influence the action of key neurotransmitters. There is also some evidence to suggest that stress and norepinephrine (NE) can also enhance the pathogenicity of certain (gram-negative, rod-shaped) bacteria!34

The human brain and gut each arise from literally the same common fetal tissue and remain forever connected through a single common thread, running all the way from the brainstem to the abdomen known as the vagus nerve – unique among mammals in humans. This telephonelike “wire” connecting the two aforementioned “tin cans” (brain and gut) provide a communication superhighway from the gut to the brain by our gut bacteria, and to some degree back the other way. An abundance of emerging research seems to show that these minute denizens have a direct and powerful influence on brain chemistry through this pathway. For instance, GABAergic pathways have been shown to be influenced by certain Lactobacillus species (rhamnosus and at least one other), which in turn may have a positive modulatory effect upon GABA expression in the brain through the vagus nerve.35

Less welcome internal riffraff occupying the small intestine in great numbers (a condition known clinically as SIBO, or small intestinal bacterial overgrowth) have been linked to numerous physiological and immunologic consequences, as well as mood symptoms such as depression.

Gut inflammation invariably begets neuroinflammation – again, our key nemesis when it comes to depression. One cannot separate the fate of one end of the vagus nerve from the other. Both gut barrier compromise and blood–brain barrier compromise occur through the same related mechanisms and are each influenced by the production of zonulin – either through the ingestion of gluten (whether one happens to have immune reactivity to it or not) or the presence of endotoxin lipopolysaccharides as a result of dysbiosis.

But as sexy as the burgeoning subject and growing body of research into the human microbiome happens to be, other aspects of digestion must also not be ignored – and without question additionally play integral roles in the health of said microbiome. One interesting recent study looking at this issue from a microbiome perspective found that, while the researchers classified humans as omnivores, human stomachs naturally have the high acidity levels normally associated with scavengers.36 Although plant foods have their decided benefits here, we are undeniably designed to be a meat-eating species, with a hydrochloric acid-based (and not a fermentative-based) digestive system. Such a diet better ensures appropriate HCl production.

Poor hydrochloric acid production and subsequent pancreatic insufficiency may additionally impair the ability to properly digest proteins and may create deficiencies of amino acids needed for hormonal/neurotransmitter production. Low HCl may also significantly impair the proper ionization and utilization of key minerals, such as zinc, magnesium, iron and others needed for healthy brain, mood, and cognitive functioning. Impaired HCl production additionally impairs production of intrinsic factor, required for digestion and absorption of vitamin B12 (deficiencies leading to macrocytic anemia, eventual neurological damage, severe memory dysfunction/dementia and mental instability, irritability, and/or paranoia).

Furthermore, biliary issues may greatly impair the digestion and absorption of fats and critical fat-soluble nutrients, further impairing mineral absorption and proper protein utilization. Digestion overall is a multidimensional avenue ripe for consideration with respect to any presenting mental health issue, and the human microbiome is but a part of this equation – albeit a highly significant one.

In short, it is simply not possible to separate digestive health from mental health issues.

Concluding Remarks

In this limited format, it is nearly impossible to encapsulate the complex etiology surrounding the epidemic phenomenon of depression. I have endeavored to touch upon some key points and issues but did not provide additional information regarding specific nutrient deficiencies, the adrenal–dysregulation connection (which I cover in depth in my e-book, Rethinking Fatigue: What your Adrenals are Really Telling You and What You Can Do About It), and the special nutritional requirements accompanying genetic metabolic conditions affecting depression in some, such as pyroluria.37 I also lacked the space to tie in my experience using neurofeedback training, which I have found to be a profound adjunct to nutritional regimens in helping to synergize the best possible functional improvements. Further information about this subject in a more clinical context can be found in the recently released academic book Restoring the Brain: Neurofeedback as an Integrative Approach to Health,

In summary, with respect to the nutritional side of things from a foundational macronutrient perspective, there is nothing at all more stabilizing to the brain than healthy, natural dietary fat … and nothing more commonly destabilizing than dietary sugar and starch (followed closely by food–sensitivity related immune reactivity). The underlying bugaboo here (it turns out) is inflammation, and “Ketone body metabolism reduces oxygen free radicals, enhances tolerance to hypoxia, and may prevent organ dysfunction from inflammatory processes.”39

The bottom line is this: The more you can come to rely on ketones as your brain’s primary source of fuel (as opposed to glucose), the healthier, less inflammatory, and more stable your brain will be and the more gracefully it will age.

A cure-all? No. But the most remarkable, solid, supportive dietary foundation upon which better mental (and physical) health may be built or ultimately even restored.

Notes

1. Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. Geneva: World Health Organization; 1996.

2. The World Health Report: 2001: Mental Health: New Understanding, New Hope. Geneva: World Health Organization; 2001.

3. WHO Mental Health Action Plan 2013–2020. Geneva: World Health Organization; 2013.

4. Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617–627.

5. Egger G, Liang G, Aparicio A, Jones, PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 27 May 2004;429:457–463; doi:10.1038/nature02625.

6. Goldberg AD, Allisemail CD, Bernstein E.Epigenetics: a landscape takes shape. Cell. 23 February 2007;128(4):635–638. doi:http://dx.doi.org/10.1016/j.cell.2007.02.006.

7. Leonard WR, Snodgrass JJ, Robertson ML. Evolutionary perspectives on fat ingestion and metabolism in humans. In: Montmayeur JP, le Coutre J, eds. Fat Detection: Taste, Texture, and Post Ingestive Effects. Boca Raton, FL: CRC Press; 2010. Chapter 1. Frontiers in Neuroscience

8. Popovich DG, Jenkins DJA, Kendall CWC, et al. The western lowland gorilla diet has implications for the health of humans and other hominoids. J Nutr. 1997;127:2000–2005.

9. Crawford MA, Bloom M, Broadhurst CL, et al. Evidence for unique function of docosahexaenoic acid during the evolution of the modern human brain. Lipids. 1999;34:S39–S47.

10. Cordain L, Watkins BA, Mann NJ. Fatty acid composition and energy density of foods available to African hominids. World Rev Nutr Diet. 2001;90:144–161.

11. Cahill GF Jr, Veech RL. Ketoacids? Good medicine?Trans Am Clin Climatol Assoc. 2003;114:149–61;discussion 162–163.

12. Gedgaudas N. Primal Body, Primal Mind: Beyond the Paleo Diet for Total Health and a Longer Life. Rochester, VT: Healing Arts Press; 2011.

13. Jacka FN, Ystrom E, Brantsaeter A, et al. Maternal and early postnatal nutrition and mental health of offspring by age 5 years: a prospective cohort study. J Am Acad Child Adolescent Psychiatry. October 2013;52(10):1038–1047. doi:http://dx.doi.org/10.1016/j.jaac.2013.07.002.

14. Plelps JR, Siemers SV, and El-Mallakh RS. The ketogenic diet for type II bipolar disorder. Neurocase. 2013; 19(5).

15. Hasselbalch SG et al. Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol. 1996;270:E746–E751.

16. Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg DJ. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol Aging. 2012 Feb;33(2):425.e19–e27. doi:10.1016/j.neurobiolaging.2010.10.006. Epub 2010 Dec 3

17. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. January 2008;9(1):46–56.

18. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med. 2002 Jan 17;346(3):180–188. Review.

19. Ji S. Wheat: 200 clinically confirmed reasons not to eat it [online article]. GreenMedInfo.com. http://www.greenmedinfo.com/blog/200-clinically-confirmed-reasons-not-eat-wheat?page=2.

20. Margutti P, Delunardo F, Ortona E. Autoantibodies associated with psychiatric disorders. Curr Neurovasc Res. 2006 May;3(2):149–157. Review

21. Matsunagab H., Kimuraa M, Tatsumia K, et al. Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders J Neuroimmunol. August 2003;141(1–2):155–164

22. Benros ME, Waltoft BL, Nordentoft M, et al. Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry. 2013;70(8):812–820. doi:10.1001/jamapsychiatry.2013.1111

23. Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA. Cognitive impairment and celiac disease. Arch Neurol. 2006 Oct;63(10):1440–1446

24. Bushara KO. Neurologic presentation of celiac disease. Gastroenterology. 2005 Apr;128(4 Suppl 1):S92–S97. Review

25. Benros et al. 2013. Op cit.

26. Maes M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry. January 1995;19(1):11–38

27. Schiepers OJG, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. February 2005;29(2):201–217.

28. Kharrazian D. Why Do I Still Have Thyroid Symptoms (When My Lab Tests are Normal)? 1st ed. Elephant Press; 2010.

29. Carta MG, Loviselli A, Hardoy MC, et al. The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future. BMC Psychiatry. 2004;4:25. doi:10.1186/1471-244X-4-25.

30. Eaton WW1, Pedersen MG, Nielsen PR, Mortensen PB. Autoimmune diseases, bipolar disorder, and non-affective psychosis. Bipolar Disord. 2010 Sep;12(6):638–646. doi:10.1111/j.1399-5618.2010.00853.x.

31. Chang KD1, Keck PE Jr, Stanton SP, McElroy SL, Strakowski SM, Geracioti TD Jr. Differences in thyroid function between bipolar manic and mixed states. Biol Psychiatry. 1998 May 15;43(10):730–733

32. Addolorato G et al. Regional cerebral hypoperfusion in patients with celiac disease. Am J Med. 2004;116(5):312–317.

33. Hallert C et al. Evidence of poor vitamin status in coeliac patients on a gluten fee diet for ten years. Aliment Pharmacol Ther. July 2002;16(7):1333–1339.

34. Lyte M, Ernst S. Catecholamine induced growth of gram-negative bacteria. Life Sci 1992;50(3):203–212.

35. Barrett E et al. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012;113:411–417.

36. Beasley DE, Koltz AM, Lambert JE, Fierer N, Dunn RR. The evolution of stomach acidity and its relevance to the human microbiome. PLoS One. 2015;10(7):e0134116. doi:10.1371/journal.pone.0134116.

37. Gedgaudas N. Rethinking Fatigue: What your Adrenals are Really Telling You and What You Can Do About It. Primal Body Primal Mind Publishing; 2014.

38. Kirk HW, ed. Restoring the Brain: Neurofeedback as an Integrative Approach to Health.

39. T N Seyfried, T M Sanderson, M M El-Abbadi, R McGowan, and P Mukherjee. “Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer. 2003 October 6; 89(7): 1375–1382.