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  GRAIN BRAIN by David Perlmutter, M.D.

 

     It difficult to overstate the impact Dr. Perlmutter's contribution to our understanding of health and the gut biome, brain health, stimulating neurogenesis and the role of inflammation in a myriad of pathologies, exposing of role of carbs in general, sugar, fructose and amylopectin A in modern dwarf wheat. He boldly promises to help with ADHD, anxiety and chronic stress, chronic headaches and migraines, depression, diabetes, epilepsy, focus and concentration problems, inflammation conditions and diseases including arthritis, insomnia, intestinal problems (celiac disease, gluten sensitivity and irritable bowel), memory problems and mild cognitive impairment (often a precursor to Alzheimer's disease), mood disorders, overweight and obesity, Tourette's syndrome and much more. Dr. Perlmutter is a luminary in restoring America to The Path to Health. Carbohydrates and processed polyunsaturaed vegetable oils, canola, corn, cottonseed, peanut, safflower and sunflower are contributing to cardiovascular disease, obesity and dementia. Diets high in saturated fats and cholesterol are good for the heart and brain. You can change your DNA with food despite your inherited genes. Although only a small percentage of the population has digestive system sensitivity to gluten, virtually everyone's brain is susceptible to a negative reaction to gluten. Diabetes and brain disease are the costliest maladies in the United States, yet they are largely preventable. Food is a powerful epigenetic modulator and can change the expression of our DNA.

     Dr. Perlmutter understands our current medical establishment where we are looking for a quick fix in the latest and greatest pill; physicians can be pill purveyors- focused on illness, not wellness and treatments are often fraught with dangerous consequences. Post menopausal women on a statin drug have a 48% greater chance of developing diabetes (which doubles the chances of Alzheimer's). 1 Babies of gluten sensitive women have an increased risk of schizophrenia and other psychiatric disorders later in life. 2 The key is a low carb high fat diet, consuming ingredients that turn on the body's own powerful antioxidant and detoxification pathways. Currently, only one percent of us will get through life with no mental impairment. He suggests the following lab work for your current assessment: Fasting glucose, HgB A1c, Fructosamine, Fasting insulin, Homocysteine, Vitamin D, C-Reactive protein and the Cyrex array 3 or 4 for gluten sensitivity.

     Back in the Paleolithic era, our ancestors ate 20% of calories from protein, just like today. But they ate 75% as fat and only 5% as carbohydrates. Today we consume 60% of our calories from carbohydrates and only 20% from fat. Now we are faced with an epidemic of diabetes and obesity, heart disease, depression, autoimmune disorders, cancer and dementia. Type II diabetes has tripled in the United States in the past 40 years. New estimates are for over 100 million humans with Alzheimer's by 2050. Just having your blood sugar on the high end of normal puts you at much greater risk for brain shrinkage. One half of Americans have 'diabesity' with 90% undiagnosed. Inflammation plays a role in virtually every chronic disease. People who used NSAID's like ibuprofen and naproxen were found to have 40% lower chance of developing Alzheimer's or Parkinson's. 3 Statins lessen brain function and increase risk of heart disease. Dr. Perlmutter tips his hat to Dr. William Davis for his seminal work Wheat Belly. Professor Marios Hadjivassiliou was instrumental in finding “Gluten Sensitivity as a Neurological Illness” in the absence of gastrointestinal involvement. Gluten breaks down in the stomach into polypeptides which can cross the blood-brain barrier and stimulate the opiate receptors causing a mild euphoria. 4 Eight thousand seniors with normal brain function were followed up to 4 years and 280 developed a form a dementia (mostly Alzheimer's). Those who never ate fish had a 37% increased chance of developing dementia, whereas those who ate fish daily had a 44% decreased risk. Butter consumption had no effect, but those who consumed olive, flaxseed or walnut oil had a 60% decreased risk. 5 High cholesterol improves memory, decreases risk of Parkinson's, protects against Lou Gehrig's and can extend longevity. 6,7,8 Low LDL increases the risk of Parkinson's by 350%, 9 Of 340,000 patients, the group with the highest consumption of saturated fat had a 19% lower risk of coronary heart disease. 10 Oxidized or glycosylated LDL robs the brain of lipid delivery (brain is 70% fat with 2% of body weight but has 25% of cholesterol) and causes atherosclerosis. A high (quality) fat low carb diet is essential for brain health. MIT researcher Stefanie Seneff contributed a critical evaluation of statins which block cholesterol synthesis. She suggests low-fat diets and statins may cause Alzheimer's. 11 Statins block the synthesis of CoQ10, decrease Vitamin D, block the sex hormones and increase all cause mortality in the elderly. “Spacedoc” Duane Graveline lost his memory to statins and in 2012 the FDA indicated statins can cause cognitive side effects. 12 Israel researchers followed 300 heart failure patients and found the highest rate of mortality in the statin using low LDL group while the higher cholesterol group had a lower risk of death. 13 Lowering cholesterol does not reduce heart attack risk; the modifiable risk factors include smoking, excess alcohol consumption, lack of aerobic exercise, overweight and a diet high in carbohydrates. Statins deplete testosterone which creates a demand for testosterone replacement therapy and ED drugs. A UK study looking at 930 men with coronary heart disease found low testosterone in 24% with a risk of death of 21% versus a risk of death of 12% in the normal testosterone group. 14

     Avoidance of sugar and high fructose corn syrup (and carbohydrates in general) is essential to lifelong brain health. Glucose can be used by every cell in the body, but fructose is metabolized by the liver and is associated with impared glucose tolerance, insulin resistance, high blood fats and hypertension leading to obesity. Gary Taubes helped illuminate the work of Dr. Robert Lustig on the toxicity of sugar. 15,16 Loius Camille Mailard described misshapen proteins by sugars in 1912, predicting an important impact on medicine. These Advanced Glycation End Products, appropriated shortened AGEs, link not only diabetes, cognitive decline and aging, but dozens of diseases sharing misfolded proteins: Alzheimer's, Parkinson's, Lou Gehrig's, type II Diabetes, cataracts, atherosclerosis, emphysema, and dementia. The prion infection diseases BSE (Mad Cow), Creutzfeldt-Jakob, Kuru and Scrapie (which turn brain into sponge) have aggressive cell to cell spread of misshapen proteins. Stanley Prusiner, who won the 1997 Nobel Prize for the discovery of prions, noted in 2012 that the amyloid-beta protein associated with Alzheimer's shares prion-like characteristics. Glycation causes any protein in the body to be less functional and cross link to other damaged proteins. Glycated proteins increase free radical production by fifty fold. To reduce the powerful relationship between free radical production, oxidative stress and cognitive decline you have to reduce the availability of sugar. A commonly tested glycated protein is hemoglobin A1C which reflects the average blood sugar over the past 3 to 4 months. The higher your Hgb A1C, not only increases your risk of coronary artery disease and stroke, the faster your rate of brain loss and risk of depression. 17 Even with normal blood sugar levels, having an elevated fasting insulin level (the only way to detect insulin resistance) increases your risk of cognitive impairment. 18

The fatter you are the smaller your brain. We have known that the most dangerous fat is visceral fat (around the abdominal organs) which is tied to not only obesity and metabolic syndrome, but also cancer, autoimmune disorders and brain disease. The obese (body mass index over 30) have a brain which looks 16 years older than those with normal weight. 19 20 To be on “The Path to Health”, there is no substitute for a low carb diet.

     One of the most astounding truths in Dr. Perlmutter's work is the gift of neurogenesis. The next time you visit your physician, ask if the adult brain can regenerate neurons. If your physician says no, send them a copy of Grain Brain and Brain Maker. If on your next visit you get the same answer, get a new doctor (find one that is skeptical of the benefit of statins). Yes, we can grow new brain cells and stimulate increased neuron connections (synapses). 21 22 Brain-Derived Neurotrophic Factor or BDNF is produced by a gene on chromosome 11 which is found to be decreased not only in Alzheimer's but also epilepsy, anorexia nervosa, depression, schizophrenia, and obsessive-compulsive disorder. For some jaw dropping examples of individuals that successfully used BDNF to remodel their brains including stroke victims that learned to speak again and people born with partial brains that rewired them to work as a whole, see Norman Doidge's book, The Brain That Changes Itself: Stories of Personal Triumph from the Frontiers of Brain Science 23

     How do we stimulate BDNF? Physical exercise, caloric restriction, ketogenic diet, curcumin (tumeric) and the Omega-3 DHA. A ketogenic diet has been used since the 1920s to treat epilepsy, but is helpful in Parkinson's, Alzheimer's, ALS, and even autism, reducing amyloid in the brain, increasing the brain protective glutathione and stimulates the growth of mitochondria. 24 25 Coconut oil, from which we derive Medium Chain Triglycerides (MCTs) also increases beta-hydroxybutyrate, the most important fat for brain energy utilization. Dr. Perlmutter points out that the huge amount of free radicals produced by the normal functioning of mitochondria cannot be neutralized by consuming Vitamin E and C or eating exotic berries, calling it “The Antioxidant Hoax”. However, a specific protein called Nrf2 is far more powerful in quenching free radicals and detoxification. It is stimulated by high levels of free radicals, but also by EPA and DHA in fish oil, curcumin in tumeric, green tea extract, silymarin (milk thistle), bacopa extract, sulforaphane (in broccoli), and ashwagandha. Coffee is one of the most powerful Nrf2 activators in nature. Although inheriting the ApoE ɛ4 gene can increase your risk of Alzheimer's, following Dr. Perlmutter's protocol can mitigate it.

     Gluten may have destructive effects on the brain even in individuals without gluten sensitivity. Dr. Perlmutter's assertion that sugars and gluten filled carbohydrates may not only be responsible for impinging our brain's long term health including chronic headaches, migraines and tic disorders, but also short-term changes in behavior, focus and concentration and depression may leave you incredulous as to how something so ubiquitous and simple in our American diet could be responsible for our declining health, but he backs it up with hard science. Attention Deficit Hyperactivity Disorder (ADHD) has been diagnosed in an increasing percentage of school-age children in the United States with a concomitant dramatic rise in the use of Ritalin and Adderall, stimulants which can lead to addiction, anxiety and occasionally psychosis. 26 Dr. Perlmutter offers a number of amazing anecdotal cases of how a low carbohydrate, gluten free diet with healthy fats (DHA, coconut oil, etc.) and probiotics (Dr. Stingl uses kefir and psyllium) “cured” not only ADHD, but autism and a number of neuropsychiatric disorders. Simply going gluten free for 6 months produced a large huge improvement in ADHD patients aged 3 to 57. 27 If you are going to drink milk, Dr. Stingl recommends organic grass-fed whole milk, but much of the dairy sold in the U.S. is not what our ancestors used. Modern Holstein dairy cows can produce not only an autism and schizophrenia tied morphine-like protein from beta-casein A1 (absent in goat and human milk and far less likely in Jersey and Guernsey cows - A2), but also dozens of reproductive hormones, allergenic proteins, antibiotics, and growth factors. A trial of eliminating modern dairy should also be considered in some cases.

     Depression is the top cause of mortality in the United States. 28 Antidepressant medications are often ineffective in mild and moderate cases and carry risks. A study in Boston of 136,000 women found antidepressant use increased the risk of stroke by 45% and all cause mortality by 32%. 29 Dr. Perlmutter notes the misguided effort to lower cholesterol with statins has increased the risk of depression and suicide. The connection between celiac disease and depression may go beyond gluten sensitivity (gluten sensitive mothers are 50% more likely to produce an offspring with schizophrenia) but also the association of gut health (producing 80-90% of the body's serotonin) as well a nutrient absorbtion. He provides numerous impressive anecdotal cases of patient improvement with a low carbohydrate diet, gluten avoidance and occasionally dairy restriction. Dr. Perlmutter suggests anyone suffering from headaches should adopt a very strict sleep-wake cycle, lose the fat, stay active, try gluten avoidance for six months and watch for a connection between MSG and migraines. It is not uncommon for people who have switched to a low carbohydrate diet to experience mood elevation.

     After three days of fasting humans break down fat into ketones, unique amongst mammals. One such ketone, beta-hydroxybuturate, is a superior fuel for the brain which also improves antioxidant function, increases mitochondria and stimulates new brain cell growth. It is easily obtained by adding coconut oil to the diet. Fasting enhances energy production and paves the way for better brain function and clarity. A ketogenic diet shares the same benefits. Dr. Perlmutter laments the fact that most physicians are focused on treatments rather than prevention. His recommended supplements are DHA, resveratrol, tumeric (curcumin), probiotics (again, Dr. Stingl recommends plain Lifeway kefir), coconut oil, alpha-lipoic acid and vitamin D.

     Physical exercise is one of the most potent ways of changing your genes. Aerobic exercise turns on the genes linked to longevity and increases BDNF decreasing the risk of Alzheimer's and reversing memory decline in the elderly. Exercise builds a brain that resists physical shrinkage and enhences cognitive flexibility. Our genome requires regular aerobic exercise to sustain life. Anthropologically, the more athletic and active humans survived passing on physiological characteristics that improved endurance including higher levels of BDNF. We evolved into a smarter, faster, more clever species. Exercise controls inflammation, increases insulin sensitivity, expands the size of the brain's memory center and increases BDNF. Even walking works, exercise need not be exhaustive to be effective. Exercise lowers hemoglobin A1C, rivalling diabetes medications. So run, swim, hike, bike or walk briskly 20 minutes a day, five days a week.

     Acheiving regular, restful sleep is essential for optimal health. One week of sleep deprivation altered the function of 711 genes including some involved in stress, inflammation, immunity and metabolism. 30 Disrupted sleep increases the risk of cognitive decline, dementia and memory problems. Leptin is an inflammatory cytokine hormone which controls mammalian metabolism, discovered in 1994. Analogous to insulin resistance, the book The Rosedale Diet takes a sweeping look at leptin resistance in weight control. Ghrelin, the hunger hormone, is the counterbalancing hormone to leptin. Ghrelin levels soar in response to inadequate sleep.

 

In a nutshell:

a. Carbohydrate Restriction

b. Exercise

c. Sleep

 

After reading Grain Brain, you will want to read Brain Maker by Dr. Perlmutter and

The End of Alzheimer's by Dr. Dale Bredesen.

 

 

1. Annie L. Culver, et al., “Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative,” Arch Internal Medicine 172. no. 2 (2012): 144-152

2. Asa Blomstrom, et al., “Maternal Antibodies to Dietary Antigens and Risk for Nonaffective Psychosis in Offspring,” Amer Journal of Psychiatry 169 (2012): 625-32

3. Walter F. Stewart,, et al., “Risk of Alzheimer's Disease and Duration of NSAID Use,” Neurology 48, no. 3 (March 1997): 626-32 AND Angelika D. Wahner, et al., “Nonsteroidal Anti-Inflammatory Drugs May Protect Against Parkinson's Disease,” Neurology 69, no.19 (November 6, 2007): 1836-42

4. Christine Zioudrou, et al., “Opioid Peptides Derived from Food Proteins (the Exorphins),” Journal of Biological Chemistry 254, no. 7 (April 10, 1979): 2446-49

5. P. Barberger-Gateau, et al., “Dietary Patterns and Risk of Dementia: The Three-city Cohort Study,” Neurology 69, no. 20 (November 13, 2007): 1921-30

6. Rebecca West, et al., “Better Memory Functioning Associated with Higher Total and Low-density Lipoprotein Cholesterol Levels in Very Elderly Subjects Without the Apolipoprotein e4 Allele,” American Journal of Geriatric Psychiatry 16, no. 9 (September 2008): 781-85

7. L. M. Lau, et al., “Serum Cholesterol Levels and the Risk of Parkinson's Disease,” American Journal of Epidemiology 164, no.10 (August 11, 2006): 998-1002

8. A. W. Weverlin-Rijnsburger, et al.,”Total Cholesterol and Risk of Mortality in the Oldest Old,” Lancet 350, no. 9085 (October 18, 1997): 1119-23

9. X. Huang, et al.,”Low LDL Cholesterol and Increased Risk of Parkinson's Disease: Prospective Results from the Honolulu-Asia Aging Study,” Movement Disorders 23, no. 7 (May 15, 2008): 781-85

10. P. W. Siri-Tarino, et al., “Meta-analysis of Prospective Cohort Studies Evaluating the Association of Saturated Fat with Cardiovascular Disease,” American Journal of Clinical Nutrition 91, no. 3 (March 2010): 535-46

11. Stephanie Seneff, “APOE-4: The Clue to Why Low Fat Diet and Statins May Cause Alzheimer's” (December 15, 2009), http://people.csail.mit.edu/seneff/alzheimers_statins.html

12. Duane Graveline, Lipitor, Thief of Memory: Statin Drugs and the Misguided War on Cholesterol (Duane Graveline, MD, 2006)

13. G. Charach, et al., “Baseline Low-density Lipoprotein Cholesterol Levels and Outcome in Patients with Heart Failure,” American Journal of Cardiology 105, no. 1 (January 1, 2010): 100-04

14. C. J. Malkin, et al., “Low Serum Testosterone and Increased Mortality in Men with Coronary Heart Disease,” Heart 96, no.22 (November 2010): 1821-25

15. R. H. Lustig, et al., “Public Health: The Toxic Truth About Sugar,” Nature 482, no. 7383 (February 1, 2012): 27-29

16. Gary Taubes, “Is Sugar Toxic?” New York Times, April 13, 2011

17. M. Hamer, et al., “Haemoglobin A1c, Fasting Glucose and Future Risk of Elevated Depressive Symptoms over 2 Years of Follow-up in the English Longitudinal Study of Ageing” Psychological Medicine 41, no 9 (September 2011): 1889-96.

18. C. Geroldi, et al., “Insulin Resistance in Cognitive Impairment: The InCHIANTI Study,” Archives of Neurology 62, no 7 (2005): 1067-72

19. C. A. Raji, et al., “Brain Structure and Obesity,” Human Brain Mapping 31, no. 3 (March 2010): 353-64

20. R. A. Whitmer, et al., “Central Obesity and Increased Risk of Dementia More Than Three Decades Later,” Neurology 71, no.14 (September 30, 2008): 1057-64

21. Charles C. Gross, “Neurogenesis in the Adult Brain: Death of a Dogma,” Nature Reviews Neuroscience 1, no. 1 (October 2000): 67-73.

22. David Perlmutter, MD and Alberto Villoldo, PhD, Power Up Your Brain: The Neuroscience of Enlightenment (New York: Viking, 2007).

23. Norman Doidge, The Brain That Changes Itself: Stories of Personal Triumph from the Frontiers of Brain Science (New York: Viking, 2007)

24. C. E. Stafstrom and J. M. Rho, “The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders,” Frontiers in Pharmacology 3 (2012): 59

25. M. Gasior, et al., “Neuroprotective and Disease-modifying Effects of the Ketogenic Diet,” Behavioral Pharmacology 17, nos. 5-6 (September 2006): 431-39

26. Alan Schwarz and Sarah Cohen, “A.D.H.D. Seen in 11% of U.S. Children as Diagnoses Rise,” New York Times, March 31, 2013.

27. M. A. Verkasalo, et al., “Undiagnosed Silent Coeliac Disease: A Risk for Underachievement?” Scandinavian Journal of Gastroenterology 40, no. 12 (December 2005): 1407-12

28. C.L.J. Murray and A. D. Lopez, “The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020,” World Health Organization, Geneva, Switzerland (1996).

29. J. W. Smoller, et al., “Antidepressant Use and Risk of Incident Cardiovascular Morbidity and Mortality Among Postmenopausal Women in the Women's Health Initiative Study,” Archives of Internal Medicine 169, no. 22 (December 14, 2009): 2128-39

30. C. S. Mӧller-Levet, et al., “Effects of Insufficient Sleep on Circadian Rhythmicity and Expression Amplitude of the Human Blood Transcriptome,” Proceedings of the National Academy of Sciences 110, no. 12 (March 19, 2013):E1132-41