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Alzheimer's Could Be Diabetes-like Illness, Study Suggests By Steven Reinberg
HealthDay Reporter 

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

WEDNESDAY, Nov. 30 (HealthDay News) -- Could Alzheimer's be a form of diabetes?


That's the tantalizing suggestion from a new study that finds insulin production in the brain declines as Alzheimer's disease advances.

"Insulin disappears early and dramatically in Alzheimer's disease," senior researcher Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital and a professor of pathology at Brown University Medical School, said in a prepared statement.

"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 signaling. This demonstrates that the disease is most likely a neuroendocrine disorder, or another type of diabetes," she added.

The discovery that the brain produces insulin at all is a recent one, and de la Monte's group also found that brain insulin produced by patients with Alzheimer's disease tends to fall below normal levels.

Now her group has discovered that brain levels of insulin and its related cellular receptors fall precipitously during the early stages of Alzheimer's. Insulin levels continue to drop progressively as the disease becomes more severe -- adding to evidence that Alzheimer's might be a new form of diabetes, she said.

In addition, the Brown University team found that low levels of acetylcholine -- a hallmark of Alzheimer's -- are directly linked to this loss of insulin and insulin-like growth factor function in the brain.

The report appears in the November issue of the Journal of Alzheimer's Disease.

In its study, de la Monte's team autopsied the brain tissue of 45 patients diagnosed with different degrees of Alzheimer's called "Braak Stages." They compared those tissues to samples taken from individuals with no history of the disease.

The team analyzed insulin and insulin receptor function in the frontal cortex of the brain, a major area affected by Alzheimer's. They found that as the severity of Alzheimer's increased, the levels of insulin receptors and the brain's ability to respond to insulin decreased.

"In the most advanced stage of Alzheimer's, insulin receptors were nearly 80 percent lower than in a normal brain," de la Monte said.

In addition, the researchers found two abnormalities related to insulin in Alzheimer's. First, levels of insulin dropped as the disease progressed. Second, insulin and its related protein -- insulin-related growth factor-I -- lose the ability to bind to cell receptors. This creates a resistance to the insulin growth factors, causing the cells to malfunction and die.

"We're able to show that insulin impairment happens early in the disease," de la Monte said. "We're able to show it's linked to major neurotransmitters responsible for cognition. We're able to show it's linked to poor energy metabolism, and it's linked to abnormalities that contribute to the tangles characteristic of advanced Alzheimer's disease. This work ties several concepts together and demonstrates that Alzheimer's disease is quite possibly a Type 3 diabetes," she said.

One expert believes declining insulin levels may be an important feature of Alzheimer's, but not the whole story.

"There is now increasing evidence primarily from observational studies that diabetes, its predecessor metabolic syndrome, and insulin resistance are implicated in increasing risk for Alzheimer's disease," said Dr. Hugh C. Hendrie. He is a professor of psychiatry and co-director of the Center for Alzheimer's Disease and Related Neuropsychiatric Disorders at Indiana University Center for Aging Research, in Indianapolis.

This study adds support to these biological hypotheses and has perhaps treatment implications for the use of certain types of anti-diabetes drugs that influence insulin resistance, Hendrie said.

"There are many other factors also implicated in Alzheimer's disease, such as hypertension and inflammation, so I think it's a bit of a stretch at the moment to describe Alzheimer's disease as an endocrinological disorder like diabetes," he said.

Another expert thinks that insulin and insulin-like growth factors may be the key to slowing the progression of Alzheimer's.

"We have shown that insulin-like growth factors regulate learning and memory," said Douglas N. Ishii, a professor in the Department of Biomedical Sciences at Colorado State University in Fort Collins. "We had shown that by blocking insulin-like growth factors in the brain you block learning and memory."

When Ishii's group treated rats with insulin-like growth factors, the researchers found that the intervention prevented the loss of both learning and memory. "In addition, we showed that insulin normally regulates brain weight in adults," he said.

"The clinical potential is that by injecting insulin-like growth factors into patients, one might be able to prevent the loss of learning and memory," Ishii said. "In particular, we have a paper coming out showing that insulin-like growth factors can not only prevent the loss of learning and memory, but prevent the loss of a protein in the brain. This may lead to the slowing down of the progression of Alzheimer's."

More information

For more on Alzheimer's disease, visit the Alzheimer's Association.

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

Major observational study points to importance of healthy diet for long-term brain health
Irvine, Calif., August 12, 2005

Adults who eat the daily recommended allowance of folates – B-vitamin nutrients found in oranges, legumes, leafy green vegetables and folic acid supplements – significantly reduce their risk of developing Alzheimer’s disease, according to results from a long-term National Institute on Aging study of diet and brain aging.

The study also found that folates appear to have more impact on reducing Alzheimer’s risk than vitamin E, a noted antioxidant, and other nutrients considered for their effect as a brain-aging deterrent.

Maria Corrada and Dr. Claudia Kawas of UC Irvine’s Institute for Brain Aging and Dementia led the effort, which analyzed the diets of non-demented men and women age 60 and older. They compared the food nutrient and supplement intake of those who later developed Alzheimer’s disease to the intake of those who did not develop the disease. It is the largest study to date to report on the association between folate intake and Alzheimer’s risk and to analyze antioxidants and B vitamins simultaneously.

Results appear in the inaugural issue of the quarterly peer-reviewed research journal, Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

“Although folates appear to be more beneficial than other nutrients, the primary message should be that overall healthy diets seem to have an impact on limiting Alzheimer’s disease risk,” said Corrada, who like Kawas started with the study while at Johns Hopkins University in Baltimore.

The researchers used data from the Baltimore Longitudinal Study of Aging to identify the relationship between dietary factors and Alzheimer’s disease risk. Between 1984 and 1991, study volunteers provided detailed dietary diaries, which included supplement intake and calorie amounts, for a typical seven-day period.

Ultimately, 57 of the original 579 participants developed Alzheimer’s disease. But the researchers found that those with higher intake of folates, vitamin E and vitamin B6 shared lower comparative rates of the disease. And when the three vitamins were analyzed together, only folates were associated with a significantly decreased risk.

In turn, no association was found between vitamin C, carotenoids (such as beta-carotene) or vitamin B-12 intake and decreased Alzheimer’s risk.

“The participants who had intakes at or above the 400-microgram recommended dietary allowance of folates had a 55-percent reduction in risk of developing Alzheimer’s,” said Corrada, an assistant professor of neurology. “But most people who reached that level did so by taking folic acid supplements, which suggests that many people do not get the recommended amounts of folates in their diets.”

Folates have already been proven to reduce birth defects, and research suggests that they are beneficial to warding off heart disease and strokes. Although folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk, they are often destroyed by cooking or processing. Because of their link to reducing birth defects, folates have been added to grain products sold in the U.S. since 1998. But even with this supplement, it is thought that many Americans have folate-deficient diets.

Recent research is beginning to show relationships between folates and brain aging. Earlier this year, Dutch scientists showed that adults who took 800 micrograms of folic acid daily had significant improved memory test scores, giving evidence that folates can slow cognitive decline.

“Given the observational nature of this study, it is still possible that other unmeasured factors also may be responsible for this reduction in risk,” said Kawas, the Al and Trish Nichols Chair in Clinical Neuroscience. “People with a high intake of one nutrient are likely to have a high intake of several other nutrients and may generally have a healthy lifestyle. But further research and clinical studies on this subject will be necessary.”

Judith Hallfrisch of the U.S. Department of Agriculture, Denis Muller with the National Institute on Aging and Ron Brookmeyer with Johns Hopkins collaborated on the study, which was originally undertaken at the Gerontology Research Center of the NIA and the Department of Neurology at Johns Hopkins. Study funding came from the Extramural Programs of the NIA.

Begun in 1958 by the NIA, the Baltimore Longitudinal Study of Aging is America’s longest-running scientific study of human aging. BLSA scientists are learning what happens as people age and how to sort out changes due to aging from those due to disease or other causes. More than 1,400 men and women are study volunteers. For more information, see:

About the University of California, Irvine: Celebrating 40 years of innovation, the University of California, Irvine is a top-ranked public university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3 billion. For more UCI news, visit
Estrogen’s antioxidant power may play key role in cerebral blood vessel health
UCI study helps identify one reason why women have lower stroke risk than men
Irvine, Calif., August 25, 2005
Estrogen’s role as an inhibitor of toxic-free radicals in cerebral blood vessels may be a key reason why premenopausal women have a lower stroke risk than men.

According to UC Irvine School of Medicine researchers, estrogen has a powerful and positive influence on women’s health by increasing the energy production efficiency of mitochondria – the tiny power plants that provide cells the energy they need to function. And in doing so, the hormone inhibits the mitochondrial production of free radical oxygen molecules. Previous studies have shown that excessive amounts of these radical elements in the body, through a process called oxidative stress, can damage blood vessels and lead to stroke or degenerative disease.

 In the UCI study, Dr. Vincent Procaccio of the Center for Molecular and Mitochondrial Medicine and Genetics and colleagues discovered estrogen receptors in vascular mitochondrial cells. To see how mitochondria functioned with deficient estrogen levels, they removed the ovaries from test rats, which suppressed any hormone influence, and identified a significant increase in radical oxygen molecule levels and a decline in the capacity for mitochondria to produce energy. In rats treated with doses of estrogen, however, vascular mitochondria produced energy more efficiently with lower amounts of damaging free radicals.

 We want to find out more how estrogen can protect blood vessels in the brain,” said Procaccio, also an assistant professor of pediatrics. “And when we gain a fuller understanding, we hopefully can figure out how best to realize potential benefits of hormone replacement therapies. Also, learning the mechanisms by which estrogen is beneficial to brain circulation may give us new ideas about how to protect against stroke.”

 Spurred by recent findings of the Women’s Health Initiative, there is growing debate over the effects of estrogen and the risk of cardiovascular disease and stroke. While women aged 30 to 50 have about five times less risk of stroke than men, this difference disappears when women reach menopause. Research studies show that estrogen protects animals from experimental stroke, but recent clinical trials with certain hormone replacement therapies in older women did not show protection from stroke.

 Study results appear on the online version of Molecular Pharmacology. Chris Stirone, Sue P. Duckles and Diana N. Krause of the UCI Department of Pharmacology assisted with the study. The National Institutes of Health provided support.
 About mitochondria

Mitochondria are the power plants of cells responsible for burning the calories in our diet with the oxygen that we breathe to generate carbon dioxide, water and the energy for our cells. The cellular energy is used for two purposes, to generate heat to maintain our body temperature and to synthesize ATP (adenosine triphosphate), a chemical form of energy which permits us to do work such as exercise, think, write, and make and repair cells and tissues.

 When the mitochondria burn our dietary fuel, they also generate a toxic by-product called oxygen radicals, the mitochondrial equivalent to the smoke generated by coal-burning power plants.  Oxygen radicals, in turn, damage the mitochondria and the surrounding cell. When sufficient oxidative damage accumulates in the mitochondria and the cell, the cell dies. Hence, the chronic level of mitochondrial oxidative stress is believed to help determine an individuals aging rate and susceptibility to a variety of diseases such as cardiovascular disease, stroke, diabetes, memory loss, forms of deafness and vision loss.

 About the Center for Molecular and Mitochondrial Medicine and Genetics

The Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG), under the direction of Douglas C. Wallace, brings together basic scientists, clinical investigators and patients at UCI to determine the causes of the common degenerative diseases, cancer and aging with special emphasis on the role of mitochondria in these processes. The result is a uniquely integrated, multidisciplinary research and clinical program that intends to expand the human horizons of medical understanding. For more information, call (949) 824-3490, or e-mail at

About the University of California, Irvine: Celebrating 40 years of innovation, the University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students, and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3 billion. For more UCI news, visit




Nutrition and Cancer
Nutrition and Heart
Nutrition and aging
Nutrition and  Diabetes
Nutrition and Anti-oxidant
Nutrition resources and links

Nutrition and Cancer

Brown rice and phenols
Recent research reveals that brown rice contains phenols that are not as present in milled white rice, and these brown rice phenols exhibit cancer-fighting characteristics. Both brown rice and rice bran contain the anti-carcinogenic compounds.
Lutein-rich foods
In a recent study, people who ate the greatest amount of lutein-rich foods experienced the lowest incidence of colon cancer. Foods rich in lutein include spinach, broccoli, tomatoes, oranges, carrots, celery, and lettuce and other leafy greens.
In cell studies, garlic has demonstrated a remarkable ability to inhibit the growth of many types of cancer, including stomach and colorectal cancers. Researchers speculate that garlic may stimulate the immune system, setting off a string of immune-supportive reactions that help the body fight disease and infection.
Green tea
According to research, people who regularly drink green tea have about half as much risk of developing stomach cancer as people who do not drink green tea. Researchers believe it may be the powerful antioxidants found in green tea that make it such a potent disease fighter.
Olive oil
Researchers believe that olive oil may have the ability to help lower your risk of colon cancer. According to studies, it may be the high concentration of squalene, a constituent of olive oil, that lends olive oil its cancer-fighting powers.
Maintaining a healthy weight 
Studies show that excess weight is associated with an increased incidence of breast, uterine, prostate, and colon cancers. But, maintaining a healthy weight appears to help fight cancer even if you've already been diagnosed. If you have been unable to lose weight on your own, talk to your healthcare provider.
Flaxseed not only helps keep you regular, but also delivers a few healthy bonuses. Studies have shown that flaxseed contains precursors to lignin, a compound believed to fight breast cancer. The nutty-tasting seed also is a good source of cholesterol-lowering soluble fiber, which is what gives flaxseed its laxative quality. Flaxseed also contains high amounts of plant compounds called phytoestrogens, as well as omega-3 fatty acids, both of which may help prevent heart disease.
Though it may not yet be a household name, kale--a green, white, and purple bunch of curly leaves--is a type of cabbage that confers similar health benefits. As with other cruciferous vegetables, kale contains natural plant chemicals that research suggests may help prevent a variety of cancers by stimulating enzymes that detoxify carcinogens. Kale also contains a high amount of potassium and calcium, both of which reduce the risk of stroke by regulating blood pressure.
By adding the Chinese cabbage bok choy to your diet, you'll be getting a healthy dose of compounds called indoles. According to research, these compounds may inhibit cancer, particularly breast cancer. Look for this leafy green cabbage in the produce aisle of your local grocery store, or in Asian food stores. 
high-fiber diet
A high-fiber diet not only helps keep your colon healthy, it may lower your risk of cancers of the throat and mouth, too. According to a recent study, people who consumed the highest amount of fiber in their diets had the lowest incidence of oral and esophageal cancers. Fiber from fruit, vegetable, and whole-grain sources appears to offer the greatest cancer-fighting benefits. 
Researchers found that incorporating cauliflower into your diet may help you stave off cancer and disease. The crunchy veggie's health benefits come from its generous supply of two little known phytochemicals, sulforaphane and indole-3-carbinol. Sulphoraphane helps rid your body of toxins before they can do real damage. Indole-3-carbinol inhibits tumor growth by reducing levels of harmful estrogens. 
According to recent studies, horseradish has properties that may prove useful in cancer prevention. Both domestic horseradish and wasabi, a Japanese variety of horseradish that is served with sushi, possess the cancer-fighting powers. 
Seaweed, or kelp
Studies have shown that seaweed, or kelp, contains powerful antioxidants that may inhibit the growth of certain cancers, most notably breast cancer. Seaweed contains high concentrations of the compound tryptophan, which apparently is responsible for the anti-carcinogenic effect. Try seaweed crumbled generously on vegetables, rice, soups, or salads. 
Shiitake mushrooms
Chinese researchers revealed that certain mushrooms contain potent cancer-fighting compounds. Shiitake mushrooms have lots of lentinan, and maitake mushrooms contain beta-glucan, both phytochemicals that can help bolster the immune system.
Beta-sitosterol and peanuts
According to research, peanuts have a high concentration of beta-sitosterol, a plant sterol that may play a protective role against colon, prostate, and breast cancer. A 1.2-ounce handful of peanuts contains approximately 50 milligrams of beta-sitosterol.  
Studies reveal that women with low blood levels of key carotenoids may have twice as much risk of developing breast cancer as women with the highest blood levels of carotenoids. To get more carotenoids into your diet, fill up on fruits and vegetables that have deep green, yellow, orange, and red hues. 
Whole-grain rye bread
New research reveals that whole-grain rye bread may help protect
against colon cancer. In a recent study, eating whole-grain rye
breads significantly reduced the participants' levels of acid compounds thought to be markers of the disease. Look for breads
that say "whole rye flour" or "whole rye meal" on the ingredients
Fresh fish
A recent study reveals that diets abundant in fresh fish are associated with a lower incidence of a rare lung cancer, adenocarcinoma. Researchers speculate that the same polyunsaturated fatty acids that make fish good for the heart also may be what make fish good for the lungs. 

Nutrition and Heart

Soy foods
Soy food such as tofu, soymilk, and edamame (fresh soybeans) contain cholesterol-lowering phytochemicals called isoflavones. Soy isoflavones may help prevent LDL (bad) cholesterol from oxidizing and sticking to artery walls. Research suggests that eating 20 to 50 grams of soy protein per day can significantly reduce LDL cholesterol.
Recent studies have revealed that guggulipid supplements could help lower your unhealthy LDL-cholesterol levels, while increasing your levels of good-for-your-heart HDL cholesterol. Guggulipid is an extract of guggul, a resin from a myrrh tree that grows in India.
Orange juice
New research reveals that drinking orange juice may boost the level of HDL (good) cholesterol in your blood. Just remember, quantity counts. Drinking at least 3 cups of orange juice per day is what's needed to increase your HDL by as much as 21%.
Sesame seeds 
Sesame seeds might inhibit the absorption and production of cholesterol in the liver, which can lower your total cholesterol level. The seeds are also a good source of monounsaturated fat, which can reduce LDL (bad) cholesterol levels and increase HDL (good) cholesterol levels. Healthy cholesterol levels can mean a healthier heart.
Lentils and folate, vitamin B
Lentils are loaded with folate. In fact, no other unfortified food contains more of the key B vitamin, which helps lower heart disease and cancer risk and protects against certain birth defects. A cup of cooked lentils in a stew or soup gives you 90% of the daily folate that you need. What's more, lentils have lots of iron, protein, and fiber
Rye bread and high fiber
when participants consumed large amounts of rye bread (about 20% of their daily caloric intake), they reduced their total serum cholesterol and lowered their LDL (bad) cholesterol.  Wheat bread, on the other hand, did not have any effect on cholesterol. The cholesterol-controlling benefit appears to come from the high fiber content of rye bread.
peas and folate
peas contain 2 times more folate--a B vitamin that may help prevent heart disease--than is found in raw spinach. And bite for bite, peas rival spinach as a source of lutein, an antioxidant that may help protect against the eye disease macular degeneration. Peas also have more fiber than cooked broccoli and are an excellent source of vitamin C.
Incorporating almonds into your diet has been shown to help reduce your risk for a heart attack by as much as 50%. This effect is likely due to the good-for-your-heart monounsaturated fats and the antioxidant vitamin E found in almonds. Monounsaturated fats can decrease your bad LDL cholesterol levels and increase your good HDL cholesterol levels. Antioxidants can help keep your arteries young. 
B vitamins
According to studies, supplementing your diet with B vitamins,
particularly B 9 (folate) and B 12, may help reduce your risk of heart disease. These vitamins help to lower blood homocysteine levels, which have been implicated in the development of cardiovascular disease. 
Calcium and vitamin D and blood pressure
If you're trying to keep your blood pressure under control, be sure to include the one-two punch of calcium and vitamin D in your diet. 
Studies show that these two nutrients together may help lower blood pressure. In a study, 80% of women who took the recommended daily amount of calcium and vitamin D experienced a significant reduction in systolic blood pressure. Only about half of the women taking calcium without vitamin D experienced a significant decrease. 
Not only do raisins abound with potassium, they also contain magnesium. Both minerals can help lower blood pressure and reduce stroke risk. Studies show that getting these minerals from fruits or vegetables may confer more benefits than getting them from supplements. 
B Vitamins 
B Vitamins Beneficial for Heart.

Nutrition and Aging 

Vitamin B12 and Folate
A recent study revealed that low blood levels of vitamin B12 and folate may be related to the development of Alzheimer's disease. In the study, people whose blood contained the lowest levels of vitamin B12 or folate were twice as likely to develop Alzheimer's disease as people with the highest levels of vitamin B12 or folate.  You should take 700 micrograms of folate and 25 micrograms of vitamin
B12 per day.
Vitamin C
According to a recent study, getting an adequate supply of vitamin C through diet is associated with a greatly reduced risk of death. Just one extra serving of vitamin C-rich food per day can lower your risk of death by as much as 20%.
4-ounce servings of fish
A recent study revealed that the omega-3 fatty acids found in fish that live in cold-water climates may prevent certain kinds of strokes. Women who ate at least two 4-ounce servings of fish per week had nearly 50% fewer incidences of thrombotic stroke than women who ate fish less frequently. 
Persimmonsare packed with twice as much cholesterol-lowering fiber as apples, which can help keep your arteries clear of fatty plaques. Persimmons also contain potassium and calcium, minerals that can help control blood pressure. 

Nutrition and Diabetes

Trans fats
A recent study revealed that eating too many trans fats may significantly increase your risk of developing type 2 diabetes. To reduce your intake of trans fats, avoid processed foods that list hydrogenated or partially hydrogenated oils at the top of their ingredients lists. 

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Nutrition and  Anti-oxidant

Vitamin E and exercise 
Although exercise is certainly good for the body, the natural increase in oxidative stress that your body experiences during strenuous exercise can harm cells. However, studies suggest that vitamin E may help reduce exercise-induced oxidative stress. It also may play a role in increasing tissue repair activity.
Although blueberries are often heralded for their antioxidant power, blackberries, strawberries, and raspberries also can hold their own in the fight against free radicals. In fact, a recent study revealed that the juice of blackberries exhibits even greater antioxidant activity than the juice of blueberries against certain free radicals.
Sweet potatoes 
Sweet potatoes contain generous amounts of the antioxidants beta carotene, vitamin C, and vitamin E. These compounds may help prevent not only cancer, but also cardiovascular disease, cataracts, and asthma.
Winter squash varieties
Winter squash varieties, such as acorn and butternut, offer a healthy dose of antioxidants, including beta carotene and vitamin C. Both nutrients may help the body recover from viral infections. Just a half-cup of winter squash contains 25% of the vitamin C and more than half the beta carotene that your body needs daily.
Pumpkin contains high concentrations of the antioxidant beta carotene, the carotenoid that helps your body fight the effects of cell-damaging free radicals, which potentially could lead to cancer. Two more carotenoids, lutein and zeaxanthin, give pumpkin even more cancer-fighting power, and also help prevent your eyes from developing cataracts.
Kiwifruit and vitamin C 
Kiwifruit is loaded with vitamin C, an antioxidant that may minimize your risk of eye diseases such as cataracts and age-related macular degeneration. Researchers speculate that the vitamin may work by protecting the lens of your eye.
sweet potato and beta carotene
Sliding a baked sweet potato onto your plate will add not only fiber to your meal, but also a healthy dose of beta carotene. Regular baked potatoes contain no beta carotene, an antioxidant that the body converts into sight-saving vitamin A.

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