New evidence shows that sugar, a highly processed diet and nitrates in food and fertilizers may be the cause of our Alzheimer's epidemic. Follow this plan to keep your brain
Like many eureka moments, it occurred by happy accident. Suzanne de la Monte, a physician scientist at Rhode Island Hospital and professor of neuropathology at The Warren Alpert Medical School of Brown University, was attempting to learn more about the effect of alcoholism on the brain, which is known to decrease insulin receptors. But to do so, she had to understand what exactly happens to neurons when these receptors are interfered with.
She injected a group of rats with a substance that disrupted the path of insulin to their brain cells, but then was surprised to discover that, in short order, her entire body of experimental rats had completely lost their memory.
When given a classic memory test requiring that they locate a platform they'd seen before, but which now lay submerged (and unseen) in murky water, the rats cast around aimlessly, unable to retrieve anything from their memory storage about where the platform might be located. Virtually overnight, their brains had turned to mush.
The rats had developed the rodent equivalent of Alzheimer's-and through this untoward result, de la Monte was handed a giant clue about the possible cause of one of the most puzzling diseases of our times.
She began to consider that Alzheimer's wasn't a matter of genes or unlucky happenstance, but a lifestyle illness, possibly a third form of diabetes-a diabetes of the brain. As with type 2 diabetes, it was a matter of the body being overwhelmed by glucose, which ultimately caused insulin resistance. Too much sugar ironically might cause a brain to starve.
From her rats, de la Monte moved on to human cadavers. After analyzing the insulin receptors in the brains of 45 cadavers who had been either normal or Alzheimer's patients at various stages of the disease, she and her team discovered that insulin expression corresponded to neurodegeneration.1
"In the most advanced stage of Alzheimer's, insulin receptors were nearly 80 per cent lower than in a normal brain," Dr de la Monte said later about her findings. She also discovered that the ability of insulin and its growth factor IGF-1 to bind to the right receptors was also impaired, ultimately causing cellular resistance to toxic proteins and leading to the death of neurons.
As we are beginning to learn, insulin plays a central role in brain signalling, which is why its absence causes immediate problems. "Insulin disappears early and dramatically in Alzheimer's disease," said de la Monte. "And many of the unexplained features of Alzheimer's, such as cell death and tangles in the brain, appear to be linked to abnormalities in insulin signalling. This demonstrates that the disease is most likely a neuroendocrine disorder, or another type of diabetes."
How your brain gets robbed by Alzheimer's
Although used as an all-purpose catchphrase, dementia could be defined as any condition in which there is an observable abnormality involving normal brain cells, or neurons, or glial cells.
But true Alzheimer's disease, as first discovered by its namesake, Alois Alzheimer, is characterized by three specific abnormalities in the brain:
senile plaques-abnormal clumps of amyloid and other sorts of proteins called 'beta-amyloid plaques' that form outside of cells in the gray matter of the brain and appear in place of normal brain cells
neurofibrillary tangles-abnormal, twisted bundles of fibres within brain neurons mostly made up of tau proteins that impair the formation of tubulin, a protein necessary for healthy connective nerve tissue, the result of which is that messages in the brain aren't transmitted properly
granulovacuolar degeneration (GVD),where neurons in the brain have abnormal 'holes' (vacuoles), each containing a small dense protein.
As the condition progresses, the brain rapidly loses brain cells and, eventually, the hippocampus and cortex-brain areas responsible for learning, memory, cognition and even personality-physically shrink.
The many faces of insulin
Up to now, doctors believed that insulin's job was simply to regulate blood sugar by alerting liver, fat and muscle cells to the location of sugar, so allowing it to be either used for energy or stored as fat. But scientists are now beginning to recognize insulin's vital role in the brain.
Insulin helps neurons in the hippocampus and frontal lobes (the brain's centre for memory and reasoning) take up glucose for neuronal energy, and regulates neurotransmitters by, for instance, stimulating the expression of choline acetyltransferase (ChAT), an enzyme responsible for making acetylcholine. A known marker of Alzheimer's disease is acetylcholine deficiency.
It also helps with the function of blood vessels that supply blood to the brain.
Finally, insulin aids the entire process of brain plasticity, where neurons are able to strengthen old connections ('neurons that fire together, wire together'), forge new ones and even change shape.
The silver tsunami
Every 68 seconds, another person in the US develops Alzheimer's disease, making it the sixth leading cause of death and one of the fastest-growing illnesses in the West (affecting 5.4 million American adults, and 26 million worldwide). Governments in the US and UK are so concerned about what has been labelled the 'silver tsunami'-the swell of Baby Boomers from the 1950s moving into older age, and the implications on society of a projected trebling of cases of dementia (to 135 million) by 2050-that health members from all the G8 leading nations met recently in London to coordinate efforts to find a successful treatment by 2025.
Towards that end, UK ministers aim to double annual research funding (to lb132 million) in those 11 years. At present, the war chest for this illness lags well behind those for other diseases like cancer, largely because of little pharmaceutical progress in coming up with a cure.
At the December conference it was revealed that, for the five drugs now on the market for Alzheimer's, drug companies have yet to produce a single clinical trial showing that the drug can reverse the course of disease, so they've essentially given up looking,
However, if de la Monte is correct and if Alzheimer's, like many of our modern degenerative diseases, has largely a one major culprit-sugar-then simple dietary management plus other promising nutrients look set to work better at preventing the disease than any pharmaceutical magic bullet.
Diabetes of the brain
Medicine has long understood the mechanics of Alzheimer's and how the development of toxic plaques eventually rob the brain of neurons (see box, left), but it's only recently that researchers like de la Monte have connected the dots and demonstrated that insulin resistance may be largely responsible.
According to de la Monte's theory, which her team and others have dubbed 'type 3 diabetes', what happens in the brain with Alzheimer's is essentially what happens to the rest of the body with diabetes.
The pancreas produces insulin to help the cells absorb the blood sugar, or glucose, needed for energy. The job of insulin is to alert the cells to the presence of sugar so it can be maximized for energy. When we eat more sugar than the cells can absorb, it gets stored as fat.
With diets high in sugar or processed carbohydrates-foods that are converted into sugar very rapidly-the body's liver, fat and muscle cells essentially begin ignoring insulin, a situation referred to as 'insulin resistance'. The pancreas, exhausted from having to pump out enough insulin to cope with overwhelming demands, begins to shut down.
Doctors like Suzanne de la Monte are discovering that a
similar situation occurs in the brain. When the body is overwhelmed with high-sugar foods, such as processed foods and fizzy drinks, this interferes with the effectiveness of insulin receptors in the brain.
And as de la Monte demonstrated, without insulin, the neurons of her rats quickly deteriorated, plaques formed and the animals showed clear signs of dementia.
One big culprit may be the Frankenstein sweetener high-fructose corn syrup (HFCS), now present in most fizzy drinks in copious amounts (see WDDTY, October 2013).
A recent study from the University of California at Los Angeles showed that rats drinking water containing HFCS had learning difficulties after just six weeks and their neurons became less responsive to insulin.2
High carbs, fewer brains
Besides the Brown University work, other empirical evidence strengthens the insulin connection. For instance, people who develop diabetes (type 2 diabetes, or lifestyle-based insulin resistance, representing 90 per cent of cases) before age 65 are more than twice as likely to develop cognitive impairment as those without the disease.3
We also know that the higher a person's carbohydrate intake, the greater the chances of developing Alzheimer's or dementia.4
Those with the so-called metabolic syndrome, a cluster of conditions associated with insulin resistance and impaired glucose metabolism, also have a higher risk of developing Alzheimer's. The British Whitehall II cohort study, carried out by a team at University College London to study the effect of quality of life on health, discovered that obese participants with the metabolic syndrome suffered far faster cognitive decline than those of normal weight or normal metabolism.5
Other lab studies are beginning to bolster de la Monte's initial findings. Research at the University of Washington in Seattle showed that rats fed a high-fat diet for a year destroyed their ability to regulate insulin levels and led to both diabetes and the development of beta-amyloid plaques in the brain (see box, page 32). As with de la Monte's rats, these animals had subsequent trouble negotiating a maze-another test of memory.
William Klein, a neurobiologist at Northwestern University in Evanston, Illinois, discovered that triggering diabetes in a group of rabbits also led to the development of Alzheimer's-like changes in the brain, including a sudden increase in beta-amyloid proteins.6
Of course, these animal studies do not necessarily apply to humans, although another extraordinary study of human tissue points to the importance of insulin in brain cells. Using brain tissue from the cadavers of both those who'd died with Alzheimer's and those who hadn't, Steven Arnold, professor of psychiatry and neurology at the University of Pennsylvania and director of the Penn Memory Center (PMC), bathed both sets of tissues in a solution of insulin. The neurons from the non-Alzheimer population initiated a chemical chain reaction as though they had been jolted back to life, whereas the neurons from Alzheimer's patients responded with just a glimmer of reaction, suggesting that, as Arnold put it, 'the insulin signalling is paralyzed'.7
One review of some 23 studies found that poor glucose tolerance is associated with cognitive impairment, particularly in verbal memory.8
And the reverse also holds true; giving patients glucose can improve long-term memory performance. In one study of 56 healthy young volunteers, receiving a drink containing 25 g of glucose led to improved memory involving the hippocampus.9
Once beta-amyloid plaques are present in the brain, these toxic proteins prevent new insulin receptors from being formed, a situation that ultimately leads to insulin resistance and a vicious cycle of more plaque formation and fewer insulin receptors.
Although ordinary insulin levels protect neurons from these toxic proteins, if the pancreas is already compromised or insulin resistance is present, these proteins will eventually run riot in the brain.
When reviewing all the evidence, de la Monte and her team found that type 2 diabetes on its own is insufficient to cause the problem, as it also requires disturbances in brain insulin and insulin-like growth factor (IGF-1). From this comes the idea that Alzheimer's is a third kind of diabetes-a 'diabetes of the brain'.
One tiny enzyme may hold the key to the connection between the usual diabetes and the one related to Alzheimer's. Both insulin and beta-amyloid are broken down by an insulin-degrading enzyme. One group of researchers studying mice with a defect in this enzyme discovered that they showed both a marked decrease in insulin broken down in the liver and elevated levels of beta-amyloid protein in the brain.10
Hold the bacon
Sugar may not be the only supermarket culprit. In de la Monte's rat study, the injection that kicked off the sudden reduction in insulin was none other than a sort of nitrosamine, a nitrate. When administered to the rats, it caused immediate cognitive impairment and disturbances in brain acetylcholine levels.
This represented another ah-ha moment for de la Monte: nitrates, present in fertilizers and in preserved foods and processed meats, may be another cause of Alzheimer's,
and she makes several compelling connections. Diabetes and fatty liver disease all skyrocketed during the years 1970-2005, when the fast-food chains' and meat-processing companies' sales increased more than eightfold, and grain-processing increased fivefold, particularly of those grains grown using nitrogen-containing fertilizers.
Nitrosamines are used as preservatives, colourings and flavourings in such foods as bacon, sausages, smoked turkey and ham, processed cheese 'food' and even beer.
Fertilizer also has high levels of added nitrates, which are absorbed by foods like grains, fruits and vegetables grown in the treated soil. When prepared at high temperatures such as frying or flame-grilling, nitrates get converted to nitrites and, eventually, to nitrosamines in the body.
Subsequent experiments by de la Monte in the lab showed that even very low, limited exposure to nitrosamines can cause Alzheimer-type brain degeneration, dementia, diabetes, fatty liver disease and obesity-a situation that was even worse when high levels of fats were added.
As with long-term exposure to highly processed high-sugar foods, de la Monte now believes that exposure to low doses of sodium nitrates through food and pesticides over years may have contributed to our present epidemics of both diabetes and Alzheimer's.
The best way to prevent Alzheimer's is to clean up your diet right now, avoiding sugary foods, processed carbohydrates that convert into sugar quickly and foods with nitrates (see box, page 35). But for those already suffering from cognitive decline with the presence of beta-amyloid plaques, is there any way to undo the damage?
Medicine has been experimenting with non-steroidal anti-inflammatories with mixed results: findings were positive for those with very mild early disease, but showed worsening of moderate full-blown disease.11
In contrast, many natural herbs and nutriceuticals have solid clinical or laboratory evidence of achieving the seemingly impossible: turning around neural damage that has already begun.
And unlike drugs that can modify symptoms, these herbs and nutrients appear to modify the entire course of disease, delaying and even reversing aspects of it.
Here are those with the most evidence of reversing the effects of insulin resistance or beta-amyloid production.
Curcumin, a compound found in the spice turmeric, used widely in Indian curries, is both a powerful antioxidant and powerful beta-amyloid buster. Lab studies show that when taken as a supplement, curcumin stops beta-amyloid molecules from forming and even disassembles them after they have formed.12 Curcumin also enhances the ability of the body's macrophages to sweep up fragments of these toxic proteins before they're allowed to reassemble.13
There's also evidence from lab studies of diabetic animals that curcumin has powerful effects by enhancing the action of insulin receptors in the brain and counteracting the effects of the nitrosamine-related agent streptozotocin, the same drug used by de la Monte in her studies (see box, above).14
Animals with Alzheimer's disease given supplements of curcumin had enhanced memory and improved performance on tests and mazes requiring memory.15
In another animal study, the spice also showed an ability to protect against ageing even after the animals were given d-galactose, a type of sugar that accelerates ageing in the brain.16
Suggested dosage: 400-800 mg/day
This natural antioxidant amino acid, present in dairy foods and meats, plays an essential role in releasing energy from fat to mitrochondria, the power pack of the cell. Animal studies show that taking supplements of l-carnitine decreases the buildup of beta-amyloid, and helps to degrade these toxic proteins and eliminate them rapidly from the body.17
In one study, Alzheimer's patients given 2-3 g of l-carnitine as supplements for three to six months experienced significantly less deterioration in cognitive function and better focus, suggesting that the amino acid retards mental decline, and particularly in younger patients.18 In another study, patients with mild dementia receiving l-carnitine for just 12 weeks had nearly three times better test scores than those taking a placebo.19
Suggested dosage: 1-3 g/day
A newly published study from the Minneapolis VA (Veterans Affairs) Health Care System of 613 patients with mild-to-moderate Alzheimer's found that patients taking 2,000 IU of vitamin E every day reduced their cognitive decline by nearly one-fifth compared with patients taking a placebo. This is the equivalent, the researchers said, of delaying disease progression by six months.
Although the researchers used alpha-tocopherol, the latest evidence suggests that high levels of gamma-tocopherols (found in tocotrienols) offer a lower risk of cognitive impairment.20
Suggested dosage: 400-2000 IU/day (preferably as tocotrienols)
This herbal root (Panax ginseng), long used in Chinese medicine as a brain-booster, also works to reduce the formation of beta-amyloid plaques and boost the body's ability to clear them. Both human and animal studies show that ginseng can reverse many of the cognitive and memory deficits usually seen in Alzheimer's.21 In one study, patients taking ginseng extracts enjoyed improved scores on standard tests for Alzheimer's,21 while in another study, patients taking 4.5 g/day of the root extract continued making improvements throughout the 12-week study.22
Suggested dosage: 400-1,000 mg/day
This natural extract of the Chinese club moss Huperzia serrata is an age-old Chinese remedy for senile dementia. It protects the mitochondria of brain cells from attack by beta-amyloid and stimulates enzymes that destroy these proteins.23 Plus it binds to the enzyme that destroys the brain neurotransmitter acetylcholine and so preserves the nerve cell's main communication system.24
This alkaloid extract has also shown extraordinary effects by producing improvements of up to 348 per cent in disease severity and daily activity levels.25 In one study, some 70 per cent of a group of 100 Alzheimer'spatients scored major improvements compared with those taking a placebo.26 Just watch out for ankle swelling and insomnia as possible side-effects.
Suggested dosage: 200-400 mg/day
The neurosteroid dehydroepiandrosterone (DHEA), the adrenal gland's most abundant hormone, is the body's natural anti-stress hormone, produced in response to the stress hormone cortisol, high levels of which have known structural and functional effects on the brain's hippocampus. As we age, levels of DHEA sharply drop, and having a lower ratio of DHEA to cortisol is a risk factor for Alzheimer's. Studies show that DHEA supplements prompt the body to produce new neurons, at least in lab experiments; in animal studies, older animals given the supplement have restored their memory and cognition to levels of their youth.27
Combine for success
Those who have successfully battled Alzheimer's, whether in the lab or in real patients, have done so by adopting a combination approach, experimenting with several kinds of nutrients and nutritional combinations to see what works best. One study of 12 institutionalized patients with entrenched later-stage disease given combinations of supplements [folic acid, vitamin B12, alpha-tocopherol vitamin E, S-adenosylmethionine (SAMe), N-acetylcysteine (NAC) and acetyl-l-carnitine] improved their standardized Alzheimer's living scores by 30 per cent, results hardly matched by any drug to date.28
Even more impressive, mice with Alzheimer's given piperine, epigallocatechin gallate (EGCG; one of the most abundant catechins in tea), alpha-lipoic acid, NAC, curcumin, B and C vitamins, as well as folic acid improved so much that their performance was indistinguishable from
that of healthy mice.29
These extraordinary results plus the breakthrough discoveries of de la Monte suggest that the epidemic of Alzheimer's is not a mystery, but another symptom of nutritional starvation, a brain finally overwhelmed by junk food.
Instead of chasing another magic bullet, funds earmarked for Alzheimer's research would best be spent educating the public about avoiding processed foods and looking into some of Mother Nature's own powerful pharmacy against functional brain loss.
Restoring your brain
To reduce your risk of Alzheimer's or improve Alzheimer's at any stage:
o Stop eating processed foods or those grown or sprayed with pesticides or fertilizer. That means avoiding all non-organic produce.
o Read labels and toss out of your shopping trolley any product that has been treated with sodium nitrate.
o Severely limit your exposure to the 'white stuff': white sugar, white rice, white and processed bread, pastas and processed stuff that comes in a box.
o Drink something besides beer, unless you can find organic varieties.
o Eat blueberries and drink coffee (3-5 cups a day)-both demonstrated to boost memory.
Take supplements of:
o Fish oils (suggested doses: 1,400 mg EPA and 1,000 mg DHA)
o High-dose B-complex vitamins (at least 1,000-5,000 mcg of B12, the brain vitamin; 250 mg of B6; at least 400 mcg of folic acid)
o Vitamin D (5,000-8,000 IU/day)
o Coenzyme Q10 (100-300 mg daily, preferably as ubiquinol)
o Magnesium (up to 600 mg/day of magnesium citrate).
o Get tested for heavy metals. Detox using Chlorella, Spirulina, daily consumption of coriander, or have chelation treatment if your levels are especially high. Heavy metals and high mercury have been implicated
Other good supplements with laboratory evidence of combatting beta-amyloid are:
o Green tea extract (up to 1,450 mg/day)
o Resveratrol (up to 250 mg/day)
o Lipoic acid (up to 480 mg/day)
o Phosphatidylserine (up to 100/day)
o N-acetylcysteine (NAC; up to 1,800 mg/day)
o Grape seed extract (150 mg/day)
o Ginkgo biloba (120-240 mg/day of standardized extract)
o Epigallocatechin gallate (EGCG)
o Vinpocetine, derived from the periwinkle plant, shown to boost levels of acetylcholine and improve learning and memory (10-30 mg/day).
J Alzheimers Dis, 2005; 7: 45-61
J Physiol, 2012; 590: 2485-99
Arch Neurol, 2008; 65: 1066-73
J Alzheimers Dis, 2012; 32: 329-39
Neurology, 2012; 79: 755-62
J Alzheimers Dis, 2012; 32: 291-305
J Clin Invest, 2012; 122: 1316-38
Neurosci Biobehav Rev, 2009; 33: 394-413
Biol Psychol, 2008; 77: 69-75
Proc Natl Acad Sci U S A, 2003; 100: 4162-7
Int J Geriatr Psychiatry, 2012; 27: 364-74
J Phys Chem B, 2012; 116: 7428-35; Biochem Biophys Res Commun, 2012; 422: 551-5
J Alzheimers Dis, 2006; 10: 1-7
Pharmacol Res, 2010; 61: 247-52; Age [Dordr], 2009; 31: 39-49
Chin Med J [Engl], 2008; 121: 832-9; Eur Neuropsychopharmacol, 2009; 19: 636-47
J Asian Nat Prod Res, 2011; 13: 42-55
J Neurosci Res, 2006; 84: 398-408
Arch Neurol, 1992; 49: 1137-41; Int Psychogeriatr, 1998; 10: 193-203
Zh Nevrol Psikhiatr Im S S Korsakova, 2011; 111: 16-22
J Alzheimers Dis, 2010; 20: 1029-37
Eur J Neurol, 2008; 15: 865-8
Alzheimer Dis Assoc Disord, 2008; 22: 222-6
Free Radic Biol Med, 2009; 46: 1454-62; Neuropsychopharmacology, 2011; 36: 1073-89
Chem Biodivers, 2011; 8: 1189-204
Ann Pharmacother, 2009; 43: 514-8
Zhonghua Yi Xue Za Zhi, 2002; 82: 941-4
Brain Res Brain Res Rev, 2001; 37: 301-12
Am J Alzheimers Dis Other Demen, 2009; 24: 27-33
PLoS One, 2010; 5: e14015