Posted
Wednesday, February 03, 2010
Britain’s dementia crisis is worse than feared and costs Britain £23bn a year – more than cancer and heart disease combined – but receives a fraction of the funding, according to a study published today.
The number of people with dementia, at 822,000, is 17% higher than has previously been estimated and will pass the 1 million mark before 2025, the Oxford university study has found.
“People do consider dementia as an inevitable part of getting old. People who reach the age of 65 have a one in three chance of having dementia before they die,” said the report’s author, Professor Alastair Gray of the university’s Health Economics Research Centre.
The true impact of dementia has been ignored for too long,” said Rebecca Wood, the Alzheimer’s Research Trust chief executive. “The UK’s dementia crisis is worse than we feared. This report shows that dementia is the greatest medical challenge of the 21st century”.
The single most exciting discovery in Alzheimer’s prevention is that the amino acid homocysteine is involved in the development of the disease. Knowing your level is one of the best ways to determine your risk before symptoms develop. But more importantly, this is a highly reversible risk factor, involving no recourse to expensive drugs or procedures – just simple dietary changes and B vitamin supplementation.
You’d think that such an important discovery would be welcomed with open arms by the medical community and governments alike but sadly the BBC report issued today, which I welcome because it does give the right message that Alzheimers can be prevented, omits the substantial evidence that the primary driver of Alzheimers is high homocysteine levels and lack of B vitamins. Homocysteine, despite being one of best indicators of risk, isn’t even mentioned. They state that the evidence for B vitamins in not ‘consistent’, yet, as you will see, the evidence is extremely consistent, suggestingthat Supplementing the right level of B vitamins may have more impact on preventing Alzheimer’s and reversing early stage memory loss than, for example, lowering your cholesterol, which the BBC report suggests despite no real evidence that lowering cholesterol will do anything to reduce risk.
In some countries, such as Germany where they run millions of tests a year, homocysteine is routinely measured. In the UK few GPs are testing it. In fact, despite over 14,000 studies now published in scientific and medical journals, chances are you’ve never even heard of homocysteine.
Homocysteine – what it is and what it does
Homocysteine is a type of amino acid produced by the body and found in the blood that, ideally, should be present in very low quantities. Problems arise, however, if you are not optimally nourished: homocysteine can accumulate in the blood, increasing the risk for over 50 diseases including heart attacks, strokes, certain cancers, osteoporosis, depression and Alzheimer’s disease.
One in two people in Britain have high homocysteine levels. But the good news is that this new and important risk factor can be reversed in weeks.
Homocysteine is produced from another amino acid, methionine, which is found in normal dietary protein. In its turn, homocysteine itself is normally turned by your body into one of two beneficial substances. These are glutathione (the body’s most important antioxidant), and SAMe, an amino acid. Problems arise when you don’t have optimal amounts of B vitamins in your diet. Then, the enzymes that turn homocysteine into these beneficial substances don’t work well enough. You can see how B vitamins lower homocysteine in this animated diagram.
To make matters more complex, it has been discovered that approximately 1 in 10 people have an inherited genetic mutation that makes them more prone to higher homocysteine levels than other people. This means that the enzyme that converts homocysteine into SAMe, known as MTHFR, doesn’t work so well. Luckily, studies show that larger daily intakes of B12 and folic acid can help to make the deficient enzyme work better.
Homocysteine – linked to Alzheimer’s since 1998
The first firm link between Alzheimer’s and homocysteine was reported in 1998, by Dr Robert Clarke and Professor David Smith from the University of Oxford, and Professor Helga Refsum, now at the University of Oslo, as part of OPTIMA (Oxford Project To Investigate Memory and Ageing). The researchers discovered high levels of homocysteine in the blood of patients who, after death, were proven to have Alzheimer’s via examination of the brain.
Since then, many different research groups have found high homocysteine levels in people suffering both age-related mental decline and Alzheimer’s. For example, a research group in Italy found that having a raised homocysteine level (above 15 µmol/l) doubled an older person’s chances of developing dementia and Alzheimer’s over a four year period. [Ravaglia G. et al., ‘Homocysteine and folate as risk factors for dementia and Alzheimer disease’1,2,3 Am J Clin Nut, 82(3):636-643 (2005)] A research group in the US reported the same findings in 2005 – the higher the homocysteine the greater was the risk of cognitive decline in older men. [Tucker K.L. et al., ‘High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study’, Am J Clin Nutr., 82(3): 627-635 (2005)]. To date, 70 out of 77 studies involving over 35,000 people have found a clear association between increasing homocysteine levels predicting increased risk of cognitive impairment and dementia or Alzheimer’s. [Smith AD The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 29(2 Suppl):S143-72 (2008)]
More recently, a growing number of indicators of Alzheimer’s-related degeneration in the brain have been shown to be directly linked to homocysteine levels. For instance, as Alzheimer’s progresses the width of the hippocampus, a vital part of the brain associated with learning and memory, shrinks. The width of the hippocampus is directly related to homocysteine levels.
Does high homocysteine cause Alzheimer’s?
So the big question is which comes first – a high homocysteine level or Alzheimer’s? Doctors from the Boston University School of Medicine neurology department wanted to answer it by determining whether homocysteine actually precedes mental decline, or occurs as a result of dementia-related B vitamin deficiencies. Their study looked at 1,092 people who had an average age of 76, did not have dementia and had already taken part in another study measuring their homocysteine levels, eight years earlier. The researchers again measured their homocysteine, and then kept track of their mental health over the next eight years. During that time, 111 developed dementia, 83 of whom were diagnosed with Alzheimer’s. The findings revealed that the higher the homocysteine levels preceding any symptoms of mental decline, the greater the risk of later developing dementia. In those with a homocysteine score of more than 14 units, the risk of Alzheimer’s almost doubled.[ 35 Seshadri S. et al., ‘Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease’, New England Journal of Medicine, 346(7):466–8 (2002). ] They concluded that ‘an increased homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer’s disease’. This powerfully suggests that optimum nutrition could, at the very least, halve your risk of developing Alzheimer’s in later years by lowering your homocysteine levels. More recently, evidence has emerged that even before there is evidence of declining mental function in so-called ‘healthy‘ elderly individuals, high homocysteine also predicts physical degeneration in certain parts of the brain.
Homocysteine doesn’t cause just mental deterioration. It also predicts physical deterioration. Research at the University of California, Los Angeles, has found that physical performance in older people, using tests of body strength, coordination, manual dexterity and gait, also declines as homocysteine levels decline.
How homocysteine damages the brain
Exactly how high homocysteine – and the inevitable B vitamin and SAMe deficiencies that always accompany it – might contribute to the kind of brain damage seen in Alzheimer’s has become a subject of heated debate in scientific circles around the world.
In Japan, Dr Matsu Toshifumi and colleagues at Tohoku University conducted brain scans on 153 elderly people and checked them against each individual’s homocysteine level. The evidence was clear – the higher the homocysteine, the greater the damage to the brain. [Toshifumi M. et al., ‘Elevated plasma homocysteine levels and risk of silent brain infarction in elderly people’, Stroke, 32:1116 (2001). ]They also confirmed that high homocysteine levels were strongly correlated with low folic acid levels.
There’s also evidence that homocysteine and its derivatives can activate certain receptors on the surface of nerve cells that result in the cell’s death. Another possible explanation is that homocysteine damages the microscopic blood vessels supplying critical brain regions, reducing blood supply and again, resulting in nerve cell death. A research group at the Baylor University Metabolic Disease Center in Dallas, Texas, led by Dr Teodoro Bottiglieri – one of the world’s leading experts on the connection between folate and mental illness – proposes that low levels of folate (which can lead to raised homocysteine levels) directly cause brain damage that triggers dementia and Alzheimer’s. Their research has found that a third of those with both dementia and high homocysteine scores (above 14 units) are deficient in folate. Dr David Snowdon at the University of Kentucky has also confirmed from autopsies that the lower the levels of serum folic acid, the greater the brain damage a person suffered.
Alzheimer’s sufferers also have less SAMe in their brains, as well as higher levels of homocysteine in their blood. SAMe, which as we’ve seen is derived from the methylation of homocysteine, is the brain’s single most important methyl donor. As such it helps to produce and activate all sorts of neurotransmitters, including the memory enhancer acetylcholine – declining levels of which are another hallmark of Alzheimer’s and a likely reason for declining memory.
Recently research has identified something you don’t want too much of called P-tau, which leads to the build up of neurofibrillary tangles, effectively nerve damage, which is one of the hallmarks of Alzheimer’s. Once again homocysteine is involved because having high homocysteine leads to the build up of toxic P-tau. [Sontag E. et al., ‘Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation’, Journal of Neuroscience. 2007 27(11):2751-9 (2007)]This might be one of the mechanisms by which homocysteine actually damages the brain, and why it is possible to prevent brain damage by lowering your homocysteine level.
Whichever way you cut it, the accumulating evidence is pointing to a consistent pattern. The higher your homocysteine score and the lower your B vitamin status, the greater your chances of declining memory, poor concentration and judgement, lowered mood, physical degeneration and poor circulation to the brain. But can you reverse the process of decay? There’s certainly good case history evidence that you can. The first double-blind controlled trial, published last year, found that you could in mild, early stage Alzheimer’s but not in the later stages. We await the results of another trial, expected by the end of the year, to see to what extent homocysteine lowering B vitamins can reverse the early signs of dementia, before an Alzheimer’s diagnosis is confirmed. I’ll keep you posted. Whatever happens you want to make sure you don’t have a high homocysteine level and do have adequate B vitamin status.
B12 and folic acid – are you really getting enough?
B12 deficiency is extremely common among people over age 60 . In a study of 61 to 87 year olds two in five people were found to be B12 deficient and the greater the deficiency the greater was the brain size shrinkage.[Vogiatzoglou A. et al., ‘Vitamin B12 status and rate of brain volume loss in community-dwelling elderly’, Neurology, 71(11): 826–832 (2008)]
However, B12 deficiency is rarely properly checked for and there’s good grounds for making it a routine test, along with homcysteine, for anyone over age 60. This is because its ability to be absorbed becomes worse with age. The usual means of checking is to measure one’s plasma B12 levels, but this is a very crude measure and it is becoming clear that having a level in the low end of the so-called ‘normal’ range is associated with worsening memory. In fact, in Japan they treat a level below 500 ng/l while, in the UK the cut off point is often 150 ng/l. Much more accurate is a test called MMA (methylmalonic acid) which is a more reliable marker for B12 deficiency and becomes high if you are deficient, or HoloTransCobalamine(HoloTC) which, if low, indicates deficiency. An MMA test is more widely available. This chemical only accumulates if you are deficient in, or not using your B12 efficiently.The greater the B12 deficiency, according to these tests, the worse is a person’s memory scores, the higher is their homocysteine level and the greater is their risk for dementia or Alzheimer’s. [Smith A.D. and Refsum H.,‘Vitamin B-12 and cognition in the elderly’, Am J Clin Nutr, 89(2): pp.707S–11S, 2009]; [Tangney C. et al., ‘Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline’ Neurology, 72(4): 361–367 (2009)]
If your homocysteine level is high it is wise to assume you are not getting enough vitamin B12.
B12 is only found in animal foods, such as meat, fish, eggs and milk. But only increasing intake of fish and milk is linked to increasing B12 levels. [Vogiatzoglou A. et al., ‘Vitamin B12 status and rate of brain volume loss in community-dwelling elderly’, Neurology, 71(11): 826–832 (2008)]
Increasing meat and eggs does not seem to be anything like as effective for improving your B12 status. My advice is to supplement at least 10mcg at any age, 50mcg if you are over 50, and 500mcg or more if you have a raised homocysteine level. The reason for recommending this seemingly very high level, given that the RDA is only 2.5µg, is that only these kind of daily intakes help to correct deficiency. That’s what a group of researchers in Holland found when they investigated how much B12 you need to take in to correct mild B12 deficiency. Only doses of 647 to 1032 µg of B12 were associated with correcting deficiency. In their words ‘the lowest dose of oral B12 required to normalize mild B12 deficiency is more than 250 times greater than the RDA, (2.5µg).’[Euseen S.J. et al., ‘Oral cyanocobalamin supplementationin older people with vitamin B12 deficiency’, Arch Intern Med, 165(10): 1167-1172 (2005)] So much for a ‘well balanced diet’ giving you all the nutrients you need!
The other homocysteine lowering B vitamin you really need to make sure you are getting enough of is folic acid which works with B12 to raise your methyl IQ. The higher your intake the lower your risk. One recent study found that, among older people, those in the top quarter of folic acid intake had half the risk of Azheimer’s. [Luchsinger J.A. et al., ‘Relation of higher folate intake to lower risk of Alzheimer disease in the elderly’, Arch Neurol, 64(1): 86-92 (2007)].
A study conducted by Jane Durga at Wageningen University in Holland, gave 818 people aged 50 to 75 either a vitamin containing 800mcg of folic acid a day, or a dummy pill. That’s almost three times the RDA and the equivalent of 2.5 pounds of strawberries a day – more than you can reasonably eat. Three years later, different aspects of intelligence were measured. On memory tests, the supplement users had scores comparable to people 5.5 years younger. On tests of cognitive speed, the folic acid helped users performed as well as people 1.9 years younger. [Durga J. et al., ‘Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial’, Lancet, 369(9557): 208-16 (2007)]
As vital as folic acid is for good methylation it is still only one of six methylation nutrients (the others being B2, B6, B12, zinc and TMG) which should always be taken together. There are good reasons for saying this. For example, the classic sign of either folic acid or B12 deficiency is tiredness. If a person is low in B12, but supplements folic acid, often the tiredness goes away but the more insidious nerve damage caused by B12, continues under the surface.
I never give folic acid alone to anyone, not even to a pregnant woman. The best way to know how much you need is to test your homocysteine level. Otherwise I’d recommend supplementing folic acid as part of a multivitamin containing at least 10mcg of B12, 20mg of B6 and 10mg of zinc.
Homocysteine – the story so far
In summary, what we already know is that:
People with Alzheimer’s consistently have high homocysteine, and low B12 and folate levels.
High homocysteine, as well as low folate and B12 status, predict a risk of developing Alzheimer’s and age-related memory problems.
High homocysteine is associated with more rapid progression of the disease.
Homocysteine levels correlate with a degree of brain damage – and the kind of damage that suggests development of dementia and Alzheimers.
High homocysteine can damage both the brain and arteries, leading to poor blood supply to the brain.
Early case studies show that giving increased amounts of homocysteine-lowering nutrients seems to arrest the progression of Alzheimer’s.
So, what’s the ‘take home’ message?
Get a handle on your homocysteine – now
The implication of all this research is that it’s a very good idea to start by measuring your homocysteine level now. This is easy to do at home, with a home test kit.
Homocysteine is measured in micromol/l, written as µmol/l. We used to think a ‘high’ level was above 15 units (µmol/l). This is what increases your risk of a heart attack and doubles your Alzheimer’s risk. Now, however, levels as low as 7 units are being linked to increased disease risk. Ideally you want a level below 6.
Supplement the right nutrients
The most powerful and quickest way to restore a normal H score, below 6 units, is to supplement specific homocysteine-lowering nutrients. These include vitamins B2, B6, B12, folic acid, trimethylglycine (TMG) and zinc and are available in combination supplements.
Follow my homocysteine lowering diet and lifestyle
A few years ago I devised the Alzheimers Prevention Plan diet – 10 easy dietary changes that will help to lower your homocysteine level. Here they are:
1. Eat less fatty meat, more fish and vegetable protein
Eat no more than four servings of lean meat a week; fish (not fried) at least three times a week; and if you’re not allergic or intolerant, a serving of a soya-based food, such as tofu, tempeh or soya sausages, or beans, such as kidney beans, chickpea hummus or baked beans, at least five times a week.
2. Eat your greens
Have at least five servings of fruit or vegetables a day. This means eating two pieces of fruit every single day, and three servings of vegetables. Vary your selections from day to day. Make sure half of what’s on your plate for each main meal is vegetables.
3. Have a clove of garlic a day
Either eat a clove of garlic a day, or take a garlic supplement every day. You can take garlic oil capsules or powdered garlic supplements.
4. Don’t add salt to your food
Don’t add salt while you’re cooking or to the food on your plate. The only salt I consider healthy is Solo salt, which has half the sodium of ordinary salt and lots of potassium and magnesium. Use this in moderation instead.
5. Cut back on tea and coffee
Don’t drink more than one cup of caffeinated or decaffeinated coffee, or two cups of tea, in a day. Instead choose from the wide variety of herbal teas and grain coffees available.
6. Limit your alcohol
Limit your alcohol intake to no more than half a pint of beer, or one glass of red wine, in a day. Ideally, limit your intake to two pints of beer or four glasses of wine a week.
7. Reduce your stress
If you are under a lot of stress, or find yourself reacting stressfully much of the time, make a decision to reduce your stress load by changing both the circumstances that are
giving you stress and your attitude. Simple solutions abound: you can do yoga, meditation and/or exercise, or see a counsellor if you have some issues to resolve. These steps can make all the difference.
8. Stop smoking
If you smoke, make a decision to stop, and seek help to do it. There is simply no safe level of smoking as far as homocysteine and your health is concerned. Smoking is nothing less than slow suicide. The sooner you stop the longer you’ll live.
This diet, lifestyle and supplement plan has the potential to halve your homocysteine score in weeks. The goal is to bring your score to below 6. (Mine is 4.5.) Your homocysteine score is probably the best objective measure of whether you are achieving optimum nutrition for you.
Chris K is a case in point. Chris K felt very unwell, with constant tiredness, worsening memory and concentration, and little zest for life. He was depressed, had no sex drive and felt brain dead. His homocysteine score was 119. He changed his diet and took homocysteine-lowering nutrients and, within three months, his homocysteine level dropped to 19. After 6 months it had dropped to 11. He cannot believe how well he now feels. His memory and concentration are completely restored. He has boundless energy from 6 a.m. until 10 p.m. He now exercises for an hour every day and has lost weight. ‘You have saved my life, or at least made it worth living again. I’m a new man and my love life has perked up,’ says Chris.
To find out more read The Alzheimer’s Prevention Plan based on cutting-edge research into nutritional medicine from experts around the world. It contains a specially formulated Alzheimer’s prevention diet and a ten-step plan to enhance your memory.
I am currently on a UK and Ireland tour talking about The Ten Secrets of 100% Healthy People which includes strategies to help prevent memory decline and dementia. To find out more click here.
The reference to Margaret Thatcher following
an early form of the GL diet is rather unfortunate
considering that she went on to develop severe
dementia/ Alzheimers disease
Posted by elizabeth rampton on 02/04 at 10:37 PM
Margaret Thatcher’s method of achieving low glycemic load and weight was eating very high protein and fat and low carbs, aka Atkins. Also, if the fats are fried that increases oxidation. I don’t think this is healthy in the long run, and hence advocate a different approach to achieving low GL, by eating lots of vegetables, less starchy carbs, a bit more protein but emphasising vegetable and fish sources of protein. ~Nuts and seeds are excellent sources of both folate, zinc and vitamin E.
This approach has a lot of potential advantages regarding Alzheimer’s prevention. It is much higher in folate and other B vitamins, as well an antioxidants and essential fats. All these factors are associated with reducing age-related memory decline.
Stress and lack of B vitamins are both known promoters of high homocysteine levels which I think is the single most important risk factor. Homocysteine can damage the brain as seen in Alzheimer’s. Maybe these factors contributed to Lady T’s demise.
Posted by patrick on 02/05 at 11:30 AM
What were the Homocysteine levels of the 1,092 eight years before? Why were they not treated with anything?. To increase B12 with fish okay but why MILK and what kind? Does Dyslexia with words or the other one for numbers, OR music in heads or those that have to whistle all the time have a brain selection problem? either to keep their brain working or for some other reason? Look forward to Patrick Holfords’ new book updating all the knowledge and research that has now come about.
Posted by cazbrice on 02/15 at 01:36 PM
I think you are referring to the the Seshadri study in 2002 in the New England Journal of Medicine charted the health of 1092 elderly people without dementia, measuring their homocysteine levels. Eight years later 111 were diagnosed with dementia, of which 83 were given the diagnosis of Alzheimer’s. Their homocysteine level at the start point covered a wide range. The point of the study was to find it if the higher homocysteine level at baseline predicted risk, which it did. Those with a level of 14+ had the greater risk. I’m sure they were treated once diagnosed.
The research shows that the amount of B12 needed to correct mild deficiency is way beyond that achievable from any food source, thus requiring supplementation (500mcg plus). The most consistent food source of B12 that correlates with lower risk is seafood as you point out. One study does find a positive association with B12 status, milk consumption and dementia risk. The type of milk wasn’t part of this research. I’d recommend at least a daily supplement containing 10mcg of B12, plus fish three or more times a week.
I am not sure about the whistling phenomena you describe. If dyslexic symptoms accrue with age certainly faulty methylation ,as well as a lack of omega 3 fats, is worth considering. The new edition of the Alzheimer’s Prevention Plan will be out in the summer. I’ll let you know when through the newsletter.
Posted by patrick on 02/15 at 03:27 PM
