Root Cause of Alzheimer’s Disease?

By Helen Papaconstantinos, RNCP, ROHP, BA

April 10, 2011 

In case you missed it, there was a great episode last Wednesday on Dr. Oz, highlighting the work of Suzanne de la Monte, MD, who is also a professor of pathology and lab medicine at the Warren Alpert Medical School of Brown University. Dr. de la Monte is one of the world’s leading Alzheimer’s researchers.

http://www.doctoroz.com/videos/alzheimers-breakthrough-pt-1

http://www.doctoroz.com/videos/alzheimers-breakthrough-pt-2

http://www.doctoroz.com/videos/alzheimers-breakthrough-pt-3

Alzheimer’s is not just about our genes. It can’t be. Since the 1970s the rates of Alzheimer’s have increased in all age groups. Something else is going on.

What Dr. de la Monte and a team of researchers at Rhode Island Hospital found was that Alzheimer’s symptoms are sparked by ‘nitrates’ – food preservative chemicals that your body uses to make nitrosamines.

The nitrate and nitrite link is still in the hypothesis stage, experts say, and there is unlikely to be just one explanation for a number of diseases. Just the same, Dr de la Monte’s hypothesis is stirring great debate.

“The theory is intriguing and worth pursuing, says neurotoxicologist Deborah Cory-Slechta, but it’s far too soon to blame nitrosamines alone for Alzheimer’s and other age-related diseases. Scientists haven’t yet documented rising rates of nitrosamines in our bodies, for one thing. And the theory may be too simplistic…Lots of other things changed in that time frame that aren’t being taken into account,” said Cory-Slechta, of the University of Rochester School of Medicine and Dentistry in New York. “I don’t think most of these kinds of complicated diseases are caused by a single factor of any kind.”

Why nitrites and nitrates? “We have reasonable evidence that human exposure to nitrosamines is at the root cause of not only Alzheimer’s, but several other insulin-resistance diseases, including Type 2 diabetes, fatty liver disease, also known as NASH, and visceral obesity” says de la Monte. [1] Nitrates irritate the liver and cause production of a toxic lipid (fat) compound that is able to cross the blood-brain barrier and destroy neuronal cells. The brain then develops insulin deficiency and insulin resistance. With no glucose (brain food), parts of the brain start to die. A scan of a brain with Alzheimer’s will show that tissue is literally missing. (More on this later). The study was published in the June 2009 Journal of Alzheimer’s Disease.[2] 

What are Nitrites and Nitrates?

Nitrites and nitrates belong to a class of chemical compounds found to be harmful to humans and animals. Over 90 percent of these tested compounds were found to be carcinogenic in various organs. They are found in many food products, including fried bacon, cured meats, cheese products, and even beer and water. Exposure also occurs through manufacturing and processing of rubber and latex products, as well as fertilizers, pesticides and cosmetics.

Sodium Nitrite (saltpeter) is commonly added to meat and fish to prevent toxin production, and to colour and flavour processed cheeses and foods such as hot dogs, bacon and cold cuts. It is responsible for the pink colour in bologna. Nitrates are often found in fertilizers which end up on produce, particularly root vegetables such as potatoes and beets. Nitrates are often added to dry-rub salting spice prior to smoking meat. Like sodium nitrate, it can also be added to brining solution to make corned beef.

How are Nitrates and Nitrites Different?

There is actually very little difference between the chemical formula for nitrates and nitrites – only an extra oxygen atom in the nitrate molecule. Think of Nitrate as ‘the mother’ and nitrite as ‘the child’. Both nitrates and nitrites form ‘Nitrosamines’. The problem occurs when nitrites and amino acids (building blocks of protein) react in the presence of heat and an acidic environment (i.e., your stomach or gut) to form carcinogenic N-nitrosamines. You can also create nitrosamines at the high temperatures needed for frying and flame-broiling.

Reducing sodium nitrite content in your food will help to reduce nitrosamine formation in your body. Avoiding cigarette smoke helps, as one of the main toxins in tobacco is a nitrosamine. Nitrates convert into nitrites. Ground beef, cured meats and bacon in particular contain abundant amounts of amines due to their high protein content.

Dr De la Monte’s research suggests that even low chronic doses of these chemicals can also have serious cumulative effects on the brain. Her study also found that the probability of dying from Alzheimer’s is far higher today than it was in 1965 for every age group. The rise in death risk was steeper with increasing age, suggesting that a longer period of exposure to the implicated chemicals made the problem worse.

Gene mutations alone cannot explain sharp rise in degenerative diseases

The authors state that the increased prevalence rates for Alzheimer’s, Parkinson’s and diabetes during the 1970 to 2005 period, cannot be explained on the basis of gene mutations. Instead they mirror the classical trends of exposure-related disease. Because nitrosamines produce biochemical changes within cells and tissues, it is conceivable that chronic exposure to low levels of nitrites and nitrosamines via processed foods, water and fertilizers, is responsible for the current epidemics of these disease, and the increasing mortality rates associated with them.

In order to arrive at this conclusion, the researchers carefully graphed and analyzed mortality rates, and compared them with increasing age for each disease. They then studied United States population growth, annual use and consumption of nitrite-containing fertilizers, annual sales at popular fast food chains, annual sales for a major meat processing company, as well as consumption of grain.

Consumption of watermelon and cantaloupe were used as a control since they are not typically associated with nitrate or nitrite exposure. After everything else was factored out, it was evident that Alzheimer’s was being sparked by something that we are eating and drinking.

De la Monte states, “If this hypothesis is correct, potential solutions include eliminating the use of nitrites and nitrates in food processing, preservation and agriculture; taking steps to prevent the formation of nitrosamines and employing safe and effective measures to detoxify food and water before human consumption.”

Alzheimer’s as a Type 3 Diabetes of the Brain:

De la Monte was the first scientist to coin Alzheimer’s as ‘Type 3 diabetes of the brain’.[3] The neurodegeneration that occurs in this type of Alzheimer’s disease suggests that impaired insulin (IGF-1 and IGF-II signaling is involved.[4] This ‘brain diabetes’ only applies to what is termed ‘sporadic Alzheimer’s’ (representing the vast majority of cases), but not to Alzheimer’s associated with a family history of the disease or the presence of a particular gene that is implicated in some cases.

If you have insulin resistance in your brain, glucose cannot get in to nourish neuronal cells and they die. In addition to brain cell death, you will also have increased levels of certain damaging enzymes, increased oxidative stress (from free radicals), advanced glycation of proteins (cooking of proteins).

Advanced levels of insulin resistance injure arterioles and capillaries, resulting in impaired blood flow and compromised function of the blood-brain barrier. This, in turn, contributes to the accumulation, of amyloid-beta, a harmful protein commonly known as senile plaque, in certain parts of the brain.

One criticism of the study is that it is not clear whether the brain changes were due to Streptozotocin, (the compound they used to inhibit local insulin production), lack of insulin, or streptozotocin causing an insult to the brain.  “To date, the construct that Alzheimer’s is type 3 diabetes remains largely unsupported,” said Dr. Sam Gandy, chairman of the Medical and Scientific Advisory Council at the Alzheimer’s Association and director of the Farber Institute for Neurosciences at Thomas Jefferson University, Philadelphia.

According to Gandy, “Streptozotocin, which causes oxidative stress, would be predicted to cause such stress in many tissues, including the brain”. Gandy also noted that the changes the researchers observed in the brains of the mice were only modest, with no clear structural pathology evident.

Can the Brain make Insulin?

During their review of the literature,  Dr. de la Monte and her researchers also sought to settle the long-standing question of whether or not insulin is produced in the brain as well as in the pancreas (Previous studies had shown  that insulin-like growth factors are produced in the brain).

Based on indirect evidence, it has long been believed that the brain produced insulin, however proof was lacking until now. In series of experiments with post-[5]mortem human brains (both normal and Alzheimer’s-afflicted), and with cell cultures from rat brains, Dr. de la Monte and her colleagues in Rhode Island showed that the brain does, in fact, synthesize insulin, as well as the insulin-like growth factors and the insulin receptors in the neuronal (brain-cell) membranes.

The experiments showed that insulin is produced in various regions of the brain (although not in the frontal cortex). The highest production is found in the hippocampus, a brain region strongly associated with memory, learning, and other cognitive functions, and in the hypothalamus, which regulates a variety of involuntary physical and emotional functions, such as sleep, mood, sex drive, and appetite.

While the brain is a prolific manufacturer of hormones, so too are other organs. For example, the pancreas and the gut produce a variety of neuroendocrine polypeptide hormones, (small-protein hormones) that act upon the nervous system. The actions of insulin in the brain therefore, do not necessarily depend on the availability of insulin from the pancreas. [6] In fact, it is entirely possible that the insulin used by the brain for glucose metabolism is ‘home-grown.’

These observations, and many others of a highly technical nature, led Dr. de la Monte and her colleagues to suggest that Alzheimer’s disease is actually a neuroendocrine disorder that resembles Type 2 diabetes but is more complex. They view it as “brain diabetes” and propose that it be called type 3 diabetes. Whether it originates in the pancreas or the brain, insulin is important to our health because of its crucial role in maintaining healthy blood sugar levels.

Fortunately, exercise and nutritional supplementation can help normalize blood sugar levels and help combat insulin resistance. Herbs and supplements that help include cinnamon (especially its MHCP component), green tea (especially its EGCG component), mulberry leaves, the antioxidants lipoic acid and quercetin, and the mineral chromium.

The ‘White-Food’ Connection:

Even if you are not consuming nitrates, Dr. de la Monte’s research shows you can still get Alzheimer’s by eating insulin-spiking ‘white foods’ such as sugar, white flour, pasta, cereals, cracker, pretzels and bread. Diabetes can take place in any part of the body – body, muscles, liver or brain. In fact, forty percent of people have diabetes that involves more than one organ.[7]

 

High Risk Foods to Avoid:

The 4 food groups that Dr. de la Monte is most concerned about regarding increased risk of Alzheimer’s include:

1. Smoked meats (bacon, smoked turkey, ham, mussels, smoked eel, etc.),

2) Processed cheeses – these are often called ‘American cheeses’. They do not melt when heated.

3) Beer – believe it or not, nitrosamines and nitrates are still being used to process some beers. Unfortunately you cannot easily find out which brands use them because these products are never listed on the ingredient labels. Just know that any processed beer will contain these products.

4) ‘White’ foods (white rice, white bread, sugar, white pasta etc.) – White foods pack a double whammy – they boost blood sugar causing inflammation in your brain and body. This leads not only to diabetes and Alzheimer’s, but cardiovascular and other diseases.[8]

 

Our Increasing Exposure to Inorganic Fertilizers

What was not discussed in the Dr. Oz episode were the strong parallels that Dr. de la Monte found between development of Alzheimer’s, Parkinson’s and Type II Diabetes, and increasing human exposure to inorganic nitrate fertilizers, the nitrites in our water supply, nitrates in the manufacture of rubber, latex products, and the cosmetics we put on our skin.

De de la Monte states, “Not only do we consume nitrates in processed foods, but they get into our food supply by leeching from the soil and contaminating water supplies used for crop irrigation, food processing and drinking.”[9]  Nitrates and nitrites are also used in the production of wines, whiskey and scotch, so you might want to avoid any type of beverage that contains these chemicals.

She and colleagues began collecting data about the use of nitrites and nitrates in fertilizers, fast food, meat and grains over the last few decades. Next they examined a national health database dating back to 1965 to find out how many people were dying from which diseases and at what ages, and how those numbers had changed.

De la Monte’s analysis showed that the use of nitrogen-containing fertilizer doubled between 1960 and 1980, right before outbreaks of insulin-resistant epidemics, including diabetes and Alzheimer’s, picked up. Additionally, sales at a fast food franchise and at a major meat processor jumped by a factor of eight since 1970. While it must be pointed out that this part of her investigation only proves ‘association’ and not direct cause, the findings are very interesting.

After factoring out everything else, de la Monte and her team had reasonable evidence to show that the spike in Alzheimer’s was not genetic – that it was caused by increased exposure to the nitrosamine compounds in not just convenience foods, but new farming practices. Her lab experiments showed that very low, limited exposures to nitrosamines (the type found in food) caused not only Alzheimer’s and Dementia, but fatty liver disease, diabetes, and obesity. Adding a high fat diet made the disease-causing effects of nitrosamines much higher, she wrote.

De la Monte had worked with a nitrosamine-like drug called streptozotocin (STZ), which scientists use in animal experiments to cause Alzheimer’s disease, diabetes mellitus and NASH (nonalcoholic steatohepatitis or ‘silent liver disease). All three of these illnesses involve resistance to insulin, a hormone that helps break down sugar. She wondered if nitrosamines in the environment might be doing the same thing to people that STZ was doing to lab animals.

Many scientific papers will say that nitrates are not harmful. They have been used in fertilizer and as a raw material for the manufacture of gun powder as far as in the late 19th century. Naturally occurring nitrites in, say green leafy vegetables, will act to help you detoxify when exposed to more harmful nitrosamines. The problem is that, over time, we have been watering our vegetables with synthetic chemical nitrates without questioning whether this is good or bad for us, and nitrates have now seeped into our water table and water supply.

Nitrates in the Global Water Supply

Nitrates, MTBE, benzene, etc. are constituents of gasoline. What are they doing in our water supply? According to the United States Environmental Protection Agency, there have been over 400,000 reported cases of petroleum-based fuels leaking from underground storage tanks.[10]

In1984 amendments to the U.S. federal Resource and Conservation Recovery Act asked that all old gasoline underground storage tanks be pulled up because they were leaking. A gasoline detergent called Tetra-Ethyl-Lead, (now outlawed), changed the molecular structure of all the underground gasoline storage tanks causing them to literally split apart at the seams. Billions of gallons of gasoline have been released into the water table over many years. Today, the degrading constituents of gasoline may be found in practically all drinking water, world-wide.

Increase in Grain crops, Fast Food and Processed Meats precedes Insulin-Resistance Epidemic

Between 1970 and 2005, grain consumption increased 5-fold. Grain crops are especially dependent on inorganic nitrate fertilizers. Nitrogen-containing fertilizer consumption doubled between 1960 and 1980 and increased by 230 percent between 1955 and 2005.

The timeline for increased consumption of nitrogen-dependent grain crops just precedes the insulin-resistance epidemic, the researchers found. The researchers also found that U.S. sales from the fast food chains and meat processing companies increased more than 8-fold from 1970 to 2005. Again, this is only an association, and does not prove a causal link, but it is very interesting.

Nitrosamines cause DNA Damage: Always Read food Labels

Look for the word ‘sodium nitrite’ on food labels. It is used as a food preservative, mainly in cured meats.

Nitrate is used mainly in inorganic fertilizers but you might find these compounds listed on processed cheese products, beer and water. Any processed beer will contain nitrates, whether or not it is listed on the label. Again, exposure also occurs through manufacturing and processing of rubber and latex products, as well as fertilizers, pesticides and cosmetics.

The role of nitrosamines has been well-studied, and their role as a carcinogen has been fully documented. Nitrosamines become highly reactive at the cellular level. This in turn, alters gene expression and causes DNA damage. The investigators proposed that the cellular alterations that occur as a result of nitrosamine exposure are fundamentally similar to those that occur with aging, Alzheimer’s, Parkinson’s and Type 2 diabetes mellitus.

De la Monte states, “All of these diseases are associated with increased insulin resistance and DNA damage. Their prevalence rates have all increased radically over the past several decades and show no sign of plateau. Because there has been a relatively short time interval associated with the dramatic shift in disease incidence and prevalence rates, we believe this is due to exposure-related rather than genetic etiologies.”

There is a press release on the Journal of Alzheimer’s Disease site which is actually entitled, “Call for reducing nitrate levels in fertilizer and water and detoxifying food and water”. In it Dr. De la Monte explains more about the dangers of nitrate and nitrite exposure to the general public more than she was able (perhaps allowed) to explain the Dr. Oz segment. If you can, please see: http://www.j-alz.com/press/2009/20090706.html

This topic is interesting but scary and controversial all at once. Dr. De la Monte will no doubt be upsetting a lot of the ‘big players’ in the food industry by asking that we avoid processed foods, eat organically grown foods (there is less nitrate in organic produce), or ask politicians to push for small farming practices. That is sure to upset the status quo. I suspect that I will also receive correspondence from those upset about having to cut back on beer, sausages and latex products. “What is left, really for us to enjoy?” they ask.

Please stay tuned to Part II of this article. It will explain what you can do to 1) Avoid getting Alzheimer’s Disease, 2) reverse early signs, 3) and help reverse Alzheimer’s Disease through diet.

[1] Dr. Suzanne De la Monte, Alzheimer’s: Diabetes of the Brain?, May 4, 2011. Available at: http://www.doctoroz.com/videos/alzheimers-diabetes-brain?page=3

[2] De la Monte, Suzanne M., Alexander Neisner, Jennifer Chu and Margit Lawton. Epidemiological Trends Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer’s Disease, Diabetes Mellitus, and Non-Alcoholic Steatophepatis. Journal of Alzheimer’s Disease, 17:3 (July 2009) pp 519-529. Retrieved April 9, 2011.

[3] Dr. De la Monte sees Alzheimer’s disease as ‘Type 3 Diabetes’ – a type of diabetes that destroys brain cells and leads to dementia. As far back as 2003, researchers at the University of Washington School of Medicine in Seattle discovered the relationship between the development of Alzheimer’s disease and disturbances in insulin and glucose metabolism, explaining why people with diabetes have a much increased chance of developing Alzheimer’s Disease. See: Watson G.S. et al, ‘The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment’, CNS Drugs, 17:27-45 (2003).

[4] Steen, E, Terry, BM, Rivera EJ, Neely, TR, Xu, XJ, Wands, JR, de la Monte, SM, Impaired insulin and insulin-like growth factor expression and signalling mechanisms in Alzheimer’s disease – is this type 3 diabetes? J  Alzheimers Dis. 2005 Feb; 7(1):63-80. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15750215?dopt=Abstract

[5] Ibid.

[6] De la Monte SM, Wands JR. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimer’s Dis 2005;7:45-61.

[7] Kash, Peter Morgan, and Jay Lombard D.O. with Tom Monte, Freedom from Disease – The Breakthrough Approach to preventions cancer, heart disease, Alzheimer’s. And Depression by Controlling Insulin. St. Martin’s Press, New York, 2008, p. 127.

[9]Lifespan (2009, July 6). Nitrates May Be Environmental Trigger for Alzheimer’s, Diabetes And Parkinson’s Disease. Science Daily. Retrieved April 10, 2011, from http://www.sciencedailu.com/releases/2009/07/090705215239.htm

[10] Water Encyclopedia, Science Issues: Pollution of Groundwater, http://www.waterencyclopedia.com/Oc-Po/Pollution-of-Groundwater.html

[11] Please visit Neonatal Paediatrician Mary T Newport’s blog for ideas on how to reverse Alzheimer’s Disease. She also discusses the insulin-resistance link to many other diseases: http://coconutketones.blogspot.com/

[12] Holford, Patrick, Shane Heaton & Deborah Colson. The Alzheimer’s Prevention Plan: 10 proven ways to stop memory decline and reduce the risk of Alzheimer’s. Piatkus Books, London, 2011.

[13] A Universities of Oxford and Oslo team found that volunteers taking these B vitamins for 2 years had 0.76% brain shrinkage, versus 1.08% shrinkage in the control group. The study was published in the September 9, 2008 issue of the journal Neurology. The research team reported an association between decreased levels of vitamin B12 and a decline in brain volume. Reduced brain volume or brain atrophy, has been associated with Alzheimer’s disease and is used as a marker for the disease’s progression.

[16] Newport, M. MD, ‘What if there was a cure for Alzheimer’s and no one knew? A Case Study by Dr. Mary Newport’, July 22, 2008. Available at: http://www.coconutketones.com/WhatIfCure.pdf

[17] Erickson KI, Raji CA, Lopez OL et al. Physical activity predicts gray matter volume in late adulthood. The Cardiovascular Health Study. Neurology, October 13 2010. Available from: http://www.neurology.org/content/early/2010/10/13/WNL.0b013e3181f88359.abstract?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Erickson&searchid=1&FIRSTINDEX=0&sortspec=date&resourcetype=HWCIT

[18] Newport, M.M.D., Op. Cit.

19] Taha, AY, Henderson, ST, Burnhan, WM. Dietary enrichment with medium chain triglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs: implications for treating age-related cognitive decline.  Neurochem Res. 2009 Sep;34(9):1619-25. Epub 2009 Mar 20. Available from:  http://www.ncbi.nlm.nih.gov/pubmed/19301124

[20] Wan-Ho, Mae, ISIS Report: Where Genes Fail – Dietary Interventions for Alzheimer’s and Parkinson’s? The Institute of Science in Society, http://www.i-sis.org.uk/wheregenesfail.php, April 25, 2001.