alzheimer.htm

A recently published randomized, double-blind, placebo-controlled, multicenter trial indicates butyrate dertivatives may improve cognitive functions.... COMMENTS from the Longevity Institute: Butyric acid is a very short chain fatty acid present only in butter and absent in vegetable oil - It appears the ban on butter and its replacement by vegetable oil may well have been a factor in the spread of Alzheimer's disease.

GENETICS, LIFESTYLE, DIET AND ALZHEIMER's DISEASE

In this newsletter we discuss the genetics of Alzheimer's disease (AD) and the hypothesis of a possible causal link between lifestyle and nutritional changes that have occurred over the last 100 years and the proliferation of AD. Further, we suggest some preventive steps.

FACTS

3 - AD cases started to multiply in the second half of the twentieth century as if it were an epidemic

COMMENTS

The condition was first described by Prof. Alzheimer in the beginning of the twentieth century. The patient described by Prof. Alzheimer had what we now describe as "early onset" AD because it appears before the age of 61 years. This is in opposition to the "late onset" form of the condition, previously described as "Senile Dementia" that develops after the age of 61 years. Today both forms are termed Alzheimer's disease altough they differ by several factors. In the early onset form the brain damage is more extensive and the evolution much faster than in the late onset form. Also in the early onset form chromosomal alterations are described ( in chromosome 21 and 14) that are missing in the later onset form. The actual increase of AD cases are late onset forms.

Today's AD numbers are staggering; About 5,000,000 people in the U.S.A. alone have the late onset condition and estimations see an increase of 350,000 cases per year in that country. (Every second, someone in America develops AD). That number 5,000,000 is expected to climb to 18,000,000 over the next 50 years.

The consequences for society and for the families are worrisome: The actual cost of Alzheimer disease (AD) for the society is around $248 billion yearly and it could quadruple before 2050. As for the family of AD patients since there is no cure for the condition, the management of the declining patient is essential and constitute a severe burden for the spouse or the caregiver with all its psychological, social, physical and financial load.

AD runs in families. However AD has a proven genetic chromosomial origin in only 2% of the cases, the “early onset AD”, where chromosomal DNA mutations have been identified.

There is no such chromosomal mutation described for the 98 other percent of the AD cases, the “late onset AD” also inaccurately named the "Sporadic Form AD”.

Then how is AD transmitted in the majority of AD cases? There must be at least one or maybe several vectors ensuring the inheritance of the condition or the transmission of some predisposing factors.

Could it be a virus? Don't scoff at it. Until not so long ago gastric ulcers were attributed to stress and a myriad of other causes until the discovery of the main causative agent: the germ Helicobacter pylori.

Until someone shows up with the proof that a virus is involved in the epidemic development of AD we are limited to utilize and try to understand the significance of what we already know about the condition and the new information provided by research.

The inheritance of AD. A recent publication may provide an explanation for the transmission of the “late onset AD”;

(quote):"Our new study shows that subjects with a mother with Alzheimer show similarities with Alzheimer's patients. They have metabolic reductions in the brain regions that are typically affected by AD, which worsen over time."

Lisa Mosconi, the author of this breakthrough discovery describes the metabolic reductions as glucose related and declares its inheritance to be of maternal origin only:

(quote):"... a reduction in glucose brain metabolism among individuals with a maternal history of the disease, but not among those with a paternal history or with neither parent affected" (end quote).

Glucose—the essential fuel of brain cells is processed in the mitochondria of the brain cells. The mitochondria are the power units of all our cells. The processing of glucose and other fuel in the mitochondria produces the energy cells need to function.

The reduction of glucose metabolism observed by Lisa Mosconi "in the brain regions that are typically affected by AD" indicates a defect in the mitochondria of the brain cells in those brain regions.

The reason the reduction in glucose brain metabolism was found exclusively "among individuals with a maternal history of the disease" is that all our mitochondria are inherited from our mother only.

A human ovule contains about 100,000 mitochondria while a spermatozoon has only 16. None of the mitochondria from the spermatozoon penetrate the ovule during fecundation. Only the nucleus of the spermatozoon enters the ovule.

It is a well known fact that each of us inherits the same amount of chromosomial genetic material (DNA) from both our parents (well not exactly: the X (the female) chromosome is bigger than the Y (the male) chromosome which makes that daughters only (with two XX's in their genome) receive equal chromosomial genetic material from both parents, while the sons (XY) have a little more from their mother). But wait: this is only valid for the genetic material contained in the chromosomes because mitochondria have their own DNA. It is called mtDNA and that genetic material comes with the mitochondria from the mother only. We all received more DNA from our mother than from our father.

A study from the University of Virginia (UV) supports the view that the defect in glucose handling by the mitochondria involves an alteration of their mtDNA;

(quote):" They found that the defective mitochondrial genes in AD cybrid cells caused increased damage from oxygen free radicals (oxidative stress), because of the inefficient processing of oxygen into water. This led to the activation of cell death pathways, which resulted in the over secretion of beta amyloid peptides and the forming of plaque-like areas in the cells ...... ........Our findings in these AD patients firmly link together defective mitochondrial genes and abnormal beta amyloid metabolism, which is the biochemical hallmark of the disease" (end quote) .

The mtDNA inherited from the mother with the mitochondria explains the maternal only inheritance of 98% of the AD cases.

Both the chromosomial DNA and the mitochondrial mtDNA have repair capacity. However the mtDNA repair mechanism is less effective because mtDNA lacks the regulatory function histone provides to the chromosomial DNA,which makes the mitochondria particularly sensible to oxidative damage and the integrity of their genome very dependent on an efficient oxidative defense system to avoid mitochondrial function loss and ultimately cell death.

Furthermore, the intimate connection between mtDNA and the inner membrane of the mitochondria makes mtDNA exquisively sensitive to any alteration of the membrane.

( quote):"Mitochondrial DNA is a particularly vulnerable target for damage due to its association with the inner mitochondrial membrane, where significant amounts of ROS (added: ROS stands for Reactive Oxygen Species) are produced, and its lack of protective histones" (end quote).

Alzheimer's Disease starts progressing when the damage becomes greater than the repair

3 - AD cases started to multiply in the second half of the twentieth century as if it were an epidemic

The twentieth century witnessed great changes in human lifespan, nutrition and lifestyle. We are not enough aware of it and if we sometimes notice it, we rapidly forget about it without realizing how profound those changes still affect all of us.

a) Human Lifespan.

During the twentieth century the human lifespan in developed countries has increased significantly. In the US the life expectancy is now 78.14 years. In the beginning of the twentieth century it was around 40 years. Since the symptoms of AD start to appear around 60-65 years of age, the almost doubling of the life expectancy has significantly contributed to the actual increase in number of AD cases. While an extended lifespan explains why we may see more cases of AD today it says nothing about the cause of the condition.

b) Nutrition

During the twentieth century the composition of our diet has changed drastically. Two important changes are the invasion of refined and "industrial" food.

1 - Sugar is an example of a refined product that has changed our diet.

Two hundred years ago refined sugar started invading an already starch-rich diet. Fifthy years ago the consumption of refined sugar in the U.S. was about 50 pounds per year for an adult and more—about 85 pounds per year, for a teenager. Since then the consumption has jumped more than 25 percent. The actual consumption of refined sugar for an average American adult is at least 64 pounds per year. For a teenager it is now more than 100 pounds per year.

(Quote) “Sugar consumption is off the charts” reports Michael F. Jacobson executive director of the Center for Science in the Public Interest, “Added sugar found largely in junk foods such as soft drinks, cakes and cookies—squeeze healthier foods out of the diet. Sugar now accounts for 16 percent of the calories consumed by an average American and 20 percent of teenagers calories.” (more)

Our biochemistry uses carbohydrates to build complex molecules. The production of complex molecules containing carbohydrates is a precise enzymatic process. When enzymes attach carbohydrates to another molecule, they attach the carbohydrate on a specific molecule and at a specific site of the molecule only. In contrast, carbohydrates can also haphazardly attach to any of several sites along any available molecule. The random attachment of a carbohydrate to other molecules is termed Glycation or Glycosylation. It happens most with the most abundant carbohydrates—glucose and fructose. Glycation occurs much more in hyperglycemia (high blood glucose).

Glycation triggers a cascade of chemical reactions that culminate in the formation, and eventual accumulation, of irreversible cross-links. Sugar “sticks” and molecules linked by random carbohydrate links loose their mobility, and their functions. Glycated armoleculese out of business. Glycation occurs all the time at a low rate. Glycation occurs much more in hyperglycemia. Glycation may happen to any molecule. If glycation happens to a molecule with a high turnover rate, the damage is temporary. However, the damaged molecule is not repaired, it is destroyed and a new one may replace it. On the contrary, the damage by the glycation of a molecule with a low turnover rate lasts longer and becomes permanent for molecules that are not replaced.

Glycation of molecules with a slow turnover (like brain cell components) is a factor of senescence—the aging of cells, tissue and organs at a faster pace than expected for the age of the person.

2 - The history of fat illustrates how food can switch from natural to "Industrial".

During hundreds of thousands of years the only fat humans could eat was animal fat and fruit fat (coconut, palm, olive) because there was nothing else available.

There is no record of an epidemic-like development of heart disease, stroke and degenerative conditions and there is no account of any prevalence of obesity, cancer, diabetes, arthritis, Alzheimer's disease, allergy and autoimmune conditions during those hundreds of thousands of years. The only epidemics occurring in the past were outbreaks of infectious diseases

Comparing the composition of human fat, animal fat and butter explains it all. Their composition is very similar. They contain the same fatty acids and in very similar proportions. How can eating what you already have in you damage your health?

READER's MANUAL

In the charts hereunder the vertical bars represent the fatty acids and the height of the bars the percentage of fatty acids in fat.

The bars for saturated fatty acids are blue, the bars for monounsaturated fatty acids are yellow and the bars for polyunsaturated fatty acids from the omega-6 essential fatty acids (n-6 EFAs) and the omega-3 essential fatty acids (n-3 EFAs) respectively red and green.

The digits at the bottom of the charts indicate the number of carbon atoms (the digits before the dot) and the number of double bonds (the digit after the dot) in the fatty acid molecule.

The data are from the United States Department of Agriculture (USDA)

A close look at the history of Margarine

Please visit the Cyberlipid Center webpage describing the history of margarine, then come back to this page.

1 - From 1869 to 1911 Margarine is a natural product

At the Cyberlipid page you have read that margarine was invented in 1869 to compensate for the scarcity of butter and animal fat (beef tallow and lard) and that margarine was initially made of beef tallow and skimmed milk and that the first addition to the original margarine was coconut oil.

2 - From 1911 to today Margarine and spreads are the main sources of trans fats in the diet

The next addition was whale oil and this addition is a tipping point in human fat consumption. The industry could use oil to make margarine and spreads only after partial hydrogenation of the oil. "The goal of partial hydrogenation is to add hydrogen atoms to cis-unsaturated fats, making them more saturated. These saturated fats have a higher melting point, which makes them attractive for baking and extends their shelving life. However, the catalyst also catalyses a side reaction that isomerizes some of the cis-unsaturated fats into trans-unsaturated fats instead of hydrogenating them completely" (From Wikipedia) Read more

(quote): "Since the early 1990s, scientific evidence has been pouring in about the many dangers of trans fats found in margarine – as well in other artificially created fats like vegetable shortening and partially hydrogenated vegetable oil" (end quote) Read more

Fat in our actual diet contains up to 3.5% of trans fatty acid and (quote): "The major sources of trans-fatty acids are bakery foods (33% of total trans-fatty acid intake), fast foods (12% of total), breads (10%), snacks (10%), and margarines/shortenings (8%)."(end quote). more .

Our biochemistry has never been exposed to such high levels of TFAs and is unable to separate TFAs from the other fatty acids.

The health deterioration caused by TFAs result from their indiscriminated incorporation into fat molecules and into the phospholipids of the cell membranes and of the membranes of the mitochondria (the power units of the cells).

Fig. 3 - Cell membranes are made of a double layer of fatty acids attached two by two

to a phosphoric acid molecule (the yellow spheres in the drawing) forming Phospholipids

In an animal experiment trans fat incorporation in the diet was found to impair brain function:

(quote) Experiments with middle-aged rats, roughly equivalent in age to a 60-year-old person, showed that after only eight weeks of eating high fat foods, those on a high trans fat diet could not perform simple memory tasks. (end quote)

The presence of TFAs in cell and mitochondria membranes disturbs the activity of the functional molecules embedded in the membrane.

1 - Such functional molecules are the calcium entry channels and calcium exit pumps.

In the membranes of heart muscle cells the calcium entry channels are activated by nerve impulse. Each new impluse allows the entry of an appropriated and small volume of calcium triggering cell activity. TFAs accumulation in the cell membrane makes the cell's calcium entry channels "leaky" allowing excessive calcium to enter the cell. Associated or not with a calcium exit pump slowdown (resulting from a long chain omega-3 essential fatty acid deficiency in the same cell membrane) calcium accumulation shall disturb the cell functions and eventually kill the cell. This mechanism explains how an excessive level of TFAs in the diet is associated with a greater risk of fatal ishaemic heart disease (IHD) and sudden cardiac death. It is estimated that dietary TFAs from partially hydrogenated oils may be responsible for between 30,000 and 100,000 premature coronary deaths per year in the United States.

Leaky calcium entry channels also accounts for the "Alzheimer's Calcium Hypothesis" formulated by a biologist of the University of Toronto.

2 - Other functional molecules embedded in cell membrane are the glucose receptors

Glucose receptors exist in all cells and are activated by the hormone insulin. TFAs in cell membrane disturb the function of the glucose receptors resulting in decreased insulin-stimulated glucose entry and disrupting cell's functions. Food glucose tends to stay in circulation triggering in response a higher insulin secretion. Excess TFAs in the diet has been linked to diabetes type II and since brain cells thrive on glucose only to Alzheimer's disease as well.

We hypothesize the reduction of glucose metabolism described by Lisa Mosconi in AD patients is related to the presence of an abnormal high level of trans fatty acids in the brain cell mitochondrial membranes where the concentration of trans fatty acids may exceed their concentration in the diet. Read more about the devastating effect of trans fatty incorporation into cell membranes

2 - Since 1950 Margarine and spreads add an excess of linoleic acid to the diet

Linoleic acid (the red bars in the charts) is an essential fatty acid. Essential Fatty Acids (EFAs) are fatty acids we cannot make and have to find in our food. There are two EFA families. The omega-6 (n-6) and the omega-3 (n-3) EFA families. Linoleic acid is from the omega-6 family. Our biochemistry uses n-6 and n-3 EFAs to make active molecules that govern cell activity. With n-6 EFAs we make molecules that stimulate cell activity, with n-3 EFAs molecules that slowdown cell activity. Health depends on this regulation and since we cannot make EFAs and have to find them in food, health also depends on the balance n-6/n-3 EFAs in the diet.

Whale oil was no longer used after 1950 owing to the international whale hunt regulation. The margarine industry had to find other sources. They chose vegetable oils. After all, they had already changed whale oil in fat and they could now use their skills to hydrogenate vegetable oil as well. Since 1950 margarine has been produced all over the world mainly from various hydrogenated vegetable oils, thus containing (like hydrogenated whale oil) trans-fatty acids and sometimes as much as up to 30% of the total fatty acid content.

It is also in the early fifties that Medicine invented its saturated fat and cholesterol myth. The oil industry jumped in that wagon advertising their products as free of cholesterol and made solely of unsaturated fat. Indeed vegetable oils (examples are corn oil, sunflower seeds and soya bean oils) contain more than 80 percent unsaturated fatty acids (yellow, red and green bars in the charts).

That percentage of unsaturated fatty acids gives vegetable oils a totally different composition than that of human fat.

Fig. 4 - Vegetable oils contain up to 60% of linoleic acid (red bars) the 18-2 omega-6 essential fatty acid

With animal products as the sole source of fat, the n-6 to n-3 ratio was about 2 to 1. Since the switch to vegetable oil with its huge linoleic acid content and the steady increase of vegetable oil consumption, the n-6 to n-3 ratio of the American diet has climbed steadily reaching today a whooping 20 to 1 instead of the recommended ratio of 2 to 1.

The active molecules (prostaglandins) our metabolism makes from n-6 EFAs increase blood coagulation, stimulate inflammation and immune reaction. The prostaglandins made from n-3 EFAs maintain blood fluidity, reduce inflammation and immune reaction.

Since our diet is the sole source of n-6 and the n-3 EFAs blood coagulation, inflammation and immune system activity are closely related to the omega-6 to omega-3 ratio in the diet.

When vegetable oils were introduced there was no interest for the n-6 to n-3 ratio in the diet and at that time no distinction was ever made between mono-unsaturated fatty acids (yellow bars) and poly-unsaturated fatty acids (red and green bars). They were all considered "healthy unsaturated". The distinction between n-6 and n-3 and the significance of the EFAs' ratio is much more recent than the introduction of vegetable oil in the diet. It is only in 1999 (four decades after the shift to vegetable oil) that the National Institute of Health (NIH) started sponsoring conferences on the role of n-3 EFAs in health and disease.

Aside from the omega-6 to omega-3 ratio disturbance, the introduction of a massive dose of linoleic acid in the diet has significantly increased the exposure of cell and mitochondrial membranes to oxidative stress. Indeed, animal fat contains about 45% of fatty acids with one double bond and less than 10% of fatty acids with more than one double bond. In contrast, vegetable oil has about 60% of fatty acids with each two double bonds and 20 % of fatty acid with one double bond . The double bonds are the weak spots in a fatty acid molecule. Double bonds are the structures where oxidative damage occurs. The switch from animal fat to vegetable oil resulted in more than a 100 percent increase of double bonds in cell membranes and consequently ina more than 100 percent increase of cell membrane and mtDNA exposure to oxidative damage.

Four generations have been flooded with trans fatty acids, and to top it off, the latter two with an excess of linoleic acid.

Although the tide is changing and research is on its way investigating the disastrous consequences of about 100 years of transfat plus 50 years of linoleic acid poisoning of our diet, we have had to wait until October 2008 to see the first publication about the effect of an arachidonic acid derivate on a mouse model of alzheimer's disease. (arachidonic acid is made exclusively from linoleic acid. The red bars in the above charts)

(quote): The most striking change discovered was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer’s disease. Arachidonic acid is thought to wreak havoc in the brains of the mice by causing too much excitation, damaging neurons. By lowering arachidonic acid levels, the researchers found they could allow neurons to function normally." (end quote)

c) Acquired Mitochondrial Damage

Considering the dietary changes that have occurred over the last century and their delerious effect on the quality and the function of the brain mitochondria (explained in the previous chapter), it is obvious that AD can appear in people with NO maternal AD inheritance and that if the person acquiring mitochondrial defect happens to be a woman she me start a new AD maternal inheritance line by transmitting damaged mitochondria to her children.

d) A Big Lifestyle Change: The Event of Artifical Light

A factor that also may have played a role in the onset of the AD epidemic is the event of artificial light.

In the latest years of the nineteenth century electricity became available for public and private use as a source of artificial light. It was a change in lifestyle that was accepted as a great improvement. Nobody realized at that time—and there is still little awareness of it today, that using artificial light after sunset has forever disrupted the natural circadian rhythms of day and night.

It may seem far-fetched at first that something apparently as trivial and unrelated to our topic as the event of artificial light could play a role in the onset of the AD epidemic. However when one considers that circadian rhythms regulate the production of the hormone melatonin, that a disruption of melatonin secretion is described in AD patients and that multiple symptoms present in AD patients are also attributed to a melatonin defect, a possible link between artificial light and the AD epidemic becomes more believable.

Melatonin is a hormone secreted by the pineal gland. Melatonin regulates several biological functions the list of which is still growing as new connections are described. Among others, it is now well established that melatonin counteracts the lipid peroxidation of cell membranes and protects chromosomal and mitochondrial DNA (mtDNA).

In animal experiments melatonin has been found to restore the secretor function, Ca2+ signals and mitochondrial potential of cells the same mitochondrial functions that are defective in AD.

Insomnia and abrupt mood change, both considered forerunners of the condition may appear years before full blown AD and are related to a reduced melatonin presence.

The secretion of melatonin crumbling with age may well be a tipping point where the effect of the inherited or acquired mitochondrial damage becomes irreversible and AD starts developing

More than 400 clinical trials have been performed or are in progress to investigate possible prevention and treatment for the condition. The National Institute on Aging Alzheimer's Disease Education & Referral Center publishes information about such 49 trials IN THE U.S.A. Most of the trials look at the possible effect of pharmaceutical drugs, Statins (of course) included.

(quote):" Finding out what causes AD's damage to brain cells provides possible avenues for new research, and hopefully the development of drugs that will reduce the abnormal oxidative stress in the mitochondria. If we can lessen cell death in AD brains, we should be able to slow the progression of the debilitating symptoms of this tragic disease." (end quote)

Among the more than 400 trials already performed or in progress only one, the PREADVICE clinical trial looks at prevention of AD with nutraceuticals: vitamin E, C and selenium. The 5 years PREADVICE clinical trial is directed by William Markesbery the director of the University of Kentucky Alzheimer's Disease Research Center (ADRC)

(quotes) " So far, vitamin E has emerged as one of the weapons we have against dementia. There are several other things you can do to lower your risk of getting Alzheimer's, but vitamin E taken in conjunction with vitamin C is important—a previous study showed that vitamin E is one factor that slows, slightly, the progression of the disease. The important thing for individuals at risk is to take vitamin E and vitamin C along with folic acid prior to getting the disease." AND "There is prior evidence that enhanced levels of selenium in the brain might increase antioxidant defense mechanisms against Alzheimer's disease. Taken together, Markesbery says, these two natural antioxidant supplements might work better than alone in fighting oxidative stress" (end quotes)

The timing of vitamin E supplementation for treating Alzheimer’s might be an important factor in its effectiveness. Vitamin E given to young transgenic mice before the formation of telltale plaques reduced up to half the levels of amyloid deposited in the brain.

It is comforting that at least one trial focusses on antioxidative elements of the diet for the prevention of AD. Vitamin E is a very good choice. Vitamin E is a fat soluble vitamin and as such can protect cell and mitochondrial membranes from oxidation. Selenium is also a very good choice because this trace-mineral, as well as manganese, is involved in DNA and mt DNA repair:

(quote) "To defend against ROS (added: ROS is short for reactive oxygen species), mitochondria metabolize superoxide and hydrogen peroxide with manganese containing superoxide dismutase and selenium-containing glutathon peroxidase, respectively" (end quote). Furthermore, a 2007 New Zealand study found an association between low hair selenium levels and cognitive decline as measured by the Timed Up and Go test (TUG)

Prevention of AD involves much more than only supplementing with vitamin E, C, manganese and selenium.

Other nutracenticals may be useful in prevention of AD. A shortage of vitamins of the B group, particularly a deficiency of vitamin B12, folic acid and vitamin B6 is a factor of arteriosclerosis. Supplementing the diet with vitamins of the B group may avoid the reduction of brain blood supply frequent in older people and an aggravating factor for AD. Vit B, vit B12 and folate concentrations correlate negatively with AD lesions. The mechanism of action may well be the vascular degradation (arteriosclerosis) associated with higher levels of Homocysteine

Then we have vitamin D which is a vitamin (or rather a steroid hormone) that has been neglected until recently. It is as if the compound were discovered again. New light is shed on vitamin D's multiple functions. (See a video about the vitamin D deficiency pandemic). People with AD like all elderly are low on vitamin D and supplementation makes good sense as well as sunbathing an hour twice weekly. (One hour full body exposure = 10,000 IU of vitamin D)

It is obvious that-due to their anti-oxidant property, vitamin E and C as well as the trace minerals selenium and manganese should play a greater role than the vitamins of the B group and than vitamin D in the prevention of AD . Their importance in protecting brain components should not bring us to forget another potent anti-oxidant and anti-imflammatory molecule which is always deficient in AD patients: the hormone melatonin. Melatonin is produced by the pineal gland situated in the brain. Melatonin is secreted during sleep. Its production crumbles with age. Older people complain of sleepiness and AD patients most. They wander around at night and are sleepy during the day.

Melatonin is considered as the "sleep hormone" because it induces sleep. However this is a trivial effect of the molecule only. The main role of melatonin is to protect brain cells: (Quote) " The researchers treated the cells with melatonin then induced cell death in rat cells similar to the way amyloid plaque causes cell death in humans. They found that cells pre-treated with melatonin had a reduced rate of death. In addition, melatonin effectively suppressed nitric oxide formation, prevented intracellular calcium overload that can occur with amyloid plaques, and significantly reduced membrane rigidity."(end quote)

Melatonin supplementation may well become as important in AD prevention as vitamin E, C, selenium, manganese, the vitamins of the B group and vitamin D. (quote):"These results supported the hypothesis that oxidative stress was an early event in AD pathogenesis and that antioxidant therapy may be beneficial only if given at this stage of the disease process. In sharp contrast to conventional antioxidants, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential therapeutic candidate in AD treatment."(end quote)

In AD prevention it makes good sense to limit the damaging effect of oxidation (and glycation) of brain cell components by supplementing the diet with the molecules cited above. However it makes equally-if not more sense, to avoid the damage to brain cells by reducing the consumption of foods that most inflict it.

The foods to avoid in AD prevention and for the reasons explained previously are refined sugar, high fructose corn syrup, all vegetable oils and-of course, all manufactured food containing them.

a - AD risk assesment

a) The maternal inheritance factor witch we like to name the Mosconi factor since the maternal inheritance of AD was first described by Lisa Mosconi, Ph.D.,M.S. People whose mother or maternal grandmother has AD are at risk of developing the condition after they reach sixty years.

b) The chromosomial factor. People that carry the chromosomal alterations described in the early onset AD form and found in about 0.04% of the population are at risk of developing the condition well before they reach 60 years.

c) The lifestyle factor . The risk of developing AD is greater in people with sleep problems.

d) The diet factor: The risk of developing AD is greater in people on a diet containing an excess of sugar, trans fatty acids and vegetable oils and deficient in long chain omega-3 essential fatty acids, anti-oxidants, minerals (particularly selenium, and manganese) and vitamins (particularly vitamin C, D, E and the vitamins of the B group).

e)The vascular factor. Arteriosclerosis of the carotide artery reducing brain blood supply aggravates AD damage.

If you are without any maternal inheritance factor for AD but with sleep problems and a bad diet that may alter the composition and the function of your brain mitochondria you may develop the condition.

Furthermore, if you are a women you can also initiate a new maternal AD lineage for your descendants.

Whatever the relative importance of the five factors described above, the damage they may cause on brain structures can be approached:

a) By a psychological evaluation comprising a mental status exam or by screening with the Geriatric Depression Scale (GDS) . A GDS provided by Drs. Wes Ashford and Anil Sharma of VA Palo Alto Health Care Systemis is available on the web for free. as well as an elementary Alzheimer's Symptoms Quiz (A"Aricept" product promotion by Pfizer). See also a list of symptoms with an an illustration of the brain indicating what symptoms are linked to the part of brain most affected.

c) By Magnetic Resonance Imaging (MRI). A new type of automated MRI scan may help detect early signs of AD in the brain decades before the first symptoms of dementia may appear.

What you can do to reduce your risk is improving or restoring your circadian rhythm, changing your diet by the reduction of vegetable oils, sugar and starch, and supplementing with n-3 EFAs, vitamins, minerals and anti-oxidants

1 - Reset your biological clock

Exposure to artificial light may have disregulated your biological clock. Light reaching your eyes triggers a nerve impulse that travels to the center of your brain and controls your biological clock. Artificial light after sunset disrupts the natural day-night cyclus. Reset your biological clock particularly if you are complaining of poor sleep. Resetting the clock involves avoiding bright light in the evening and getting ALL light out of your bedroom. Your brain produces melatonin only when informed of darkness .

Poor sleep, agitated sleep with anxiety and frequent awakening as well as difficulty to fall asleep are related to a melatonin deficiency.

The following is an excerpta from the "Hormone Handbook" by Dr. Thierry Hertoghe . (quote) "Melatonin deficiency not only includes sleep complains but also fatigue during the day, abdominal pain related to intestinal overactivity, tense muscles, restless leg syndrome, anxiety , lack of serenity, of peace of mind, depression, seasonal affective disorders, irritability and emotional instability, hypertension, premature aging and intense jet lag symptoms when crossing from a time zone to another. (end quote) Dr. Hertoghe also cites Alzheimer's disease in his list of disease susceptibility for people with melatonin deficiency.

USING MELATONIN: Start with 0.1 mg of melatonin under the tongue 15-30 minutes before bedtime. Should this not work, take 0.2 mg the next day. Increase the daily dosage by increments of 0.1 mg until your reach your optimal level. It may take a few weeks before you feel some effect and three months is the average timespan to reset your biological clock.

An overdosage of melatonin produces a short and deep sleep during 3 to 4 hours (with nightmare) followed by strong heart beat, profuse sweating and 24 hours of heavyheadness.

2 - Change your diet

a) Suppress your transfat and excessive linoleic acid intake by staying away from vegetable oils. Instead revert to butter, beef tallow, lard and fruit oils (olive, palm. coconut). Reduce the intake of sugar and of food with a high glycemic index

b) Fry meat, eggs, fish and other food at low temperature in butter or fruit oils (best is coconut)

3 - Take supplements

a) Add fish oil to your vitamin regimen to increase your long chain omega-3 EFAs intake.

b) Make a habit of taking daily a good mix of vitamins and minerals providing in particular vitamin C: 200 mg/ day, vit D: 2.000 IU/ day, vit B 12: 500 micrograms/ day, vitamin B6: 25 mg/day, Folic acid: 2.5 mg/ day, selenium: 100 microgram/ day per 60 lb bodyweight with a maximum of 300 micrograms per day, manganese: 5 mg/ day, calcium 400 mg/ day

4 - Stay away from Statins

5 - Your brain blood supply

Should you have had some brain blood supply problems like a transient ischemic attack, have your carotide arteries blood flow checked

More info

For a more customized nutritional and supplement advice than the above e-mail your request to the author of this page