Sunday, 8 March 2009

Look after your brain.

"One in three people over 65 will die with dementia..." said Dr Susanne Sorensen, head of research at the Alzheimer's Society. I read this in a recent BBC News article Vitamin D 'is mental health aid' which referred to the study Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment.
The article contained the usual phrase "...more work was needed..."

The above article also led to Parkinson's linked to vitamin D which referred to the study Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. "However, the Emory University researchers do not yet know if the vitamin deficiency is a cause or the result of having Parkinson's". "Further research is required...." yet again.

It's like someone standing by their broken-down car wondering whether it's the empty fuel tank that's made the car stop or whether it's the car stopping that's made the fuel tank empty. Does it matter? Just put some fuel in the tank and see what happens! See also Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease.

Severe Mental Impairment blights the lives of many old people and their loved ones. My mum developed Parkinson's Disease a few years ago. I didn't know anything about the condition at the time, but it's caused by the formation of Lewy Bodies (blobs of abnormally-folded alpha-synuclein protein) in the substantia nigra part of the brain, which controls movement. This part of the brain has high levels of the Vitamin D receptor. I don't know why the brain contains Vitamin D receptors, but I think that they'd like to receive some Vitamin D!

As Lewy Bodies form in other parts of the brain, mental faculties decline. The hippocampus is involved with short-term memory. The neocortex is involved with concious thought.

Mum started showing obvious signs of mental impairment in August 2007. She was assessed by a Community Psychiatric Nurse (CPN) in January 2008 when she scored 14/30 in a MMSE. She was unable to remember 3 words or follow 2 simple instructions in a row (e.g. fold this piece of paper in half and put it on the floor). I started her on 5,000iu/day of Vitamin D3, as it was having a positive effect on my mental function. She was prescribed Aricept, starting at 5mg/day for a month then increasing to 10mg/day. In May 2008 she was re-assessed and scored 26/30 in a MMSE. EDIT: In 2010, Mum's consultant told me that Aricept increases MMSE score by 3 points on average.

Unfortunately, Aricept has side-effects including severe diarrhoea and worsening of the symptoms of Parkinson's Disease, which she complained about, so her Aricept dose was reduced back down to 5mg/day.

Unsurprisingly, this resulted in a slight decline in mum's mental faculties. In November 2008, I increased her intake of smoked salmon to about 400g/week, as the consumption of long-chain omega-3 pufas have benefits. See
Low Plasma N-3 Fatty Acids and Dementia in Older Persons: The InCHIANTI Study.

After about four weeks, this had a noticeable (by myself and mum's friend) positive effect on her mental faculties so, inspired by Dr Art Ayers, I started her on Turmeric (curcumin) extract and Goldenseal (berberine) extract. See
Curcumin inhibits aggregation of alpha-synuclein
Neuroprotective effects of curcumin
Alpha-synuclein assembly as a therapeutic target of Parkinson's disease and related disorders
Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model
Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers
Research on the mechanism of neuronal apoptosis in Alzheimer's disease and the effects of tetrohydroberberine on the apoptosis... and
Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer's disease.

On January 12th 2009, mum was re-assessed and scored 26/30 in a MMSE. I thought that this was impressive considering that a) she was taking half the dose of Aricept, compared to when she previously got that score, b) she had no adverse effects from taking any of the supplements and c) she was 8 months older and degenerative brain diseases always worsen with the passage of time.

I mentioned to the CPN who did the MMSE that I was starting mum on 15mg/week Vitamin K2 as there were benefits. See
Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain ,
Vitamin K status influences brain sulfatide metabolism in young mice and rats ,
Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis and
The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease
I don't know what sphingolipids are (I know who probably does) but sulfatides are good and ceramides are bad.

Around the time that mum collapsed, I received a copy of a letter from the CPN to mum's GP which stated "I have informed him (i.e. me) that I am unaware of any robust evidence that these substances are of any benefit." However, there is no evidence that these substances are of any harm.

And finally......
What started the cascade of confusion and collapse leading to hospitalisation and discharge to a nursing home was a simple Urinary Tract Infection UTI) of e. coli. I don't know why UTIs cause so much confusion in elderly people, but elderly females are at a high risk of developing UTIs because a) elderly people don't drink enough so they don't pass enough urine, b) females have insufficient spacing between anus & urethra and c) elderly females who have any urinary/faecal leakage wear a Tena disposable "nappy/diaper", which increases the likelihood of faeces entering the urethra.

To reduce the risk of further UTIs, I have supplied the nursing home with a pot of D-mannose Plus, which contains D-mannose and cranberry extract, with instructions to add a heaped teaspoonful to a glass of juice once a week. See Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex,
Natural approaches to prevention and treatment of infections of the lower urinary tract and
Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder.


EDIT: Thanks to Galina L for bringing the following study to my attention.
Magnesium supplementation in the treatment of dementia patients.
It's probably of no help to Lewy Body Dementia sufferers, as they already have high Mg levels in their CSF. See CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.

Continued on Look after your brain, Part 2.

18 comments:

Dr. Art Ayers said...

Nigel,
The nutritional support that you outline hear is sensible and evidence based. It is also unusually low in negative side-effects. It is strange that healthcare providers are so reluctant to try nutritional approaches that are supported by evidence, but prefer their professional organization practices that are based on opinions of prominent authorities. Sad.

I would like your opinion on nutritional guidelines for my daughter, who is on a college crew team. She is strong for her weight, but can't continue to gain. She practices 4-6 hr/d. Advice?

Thanks for the shout out. Hope your mum continues to improve.

Nigel Kinbrum BSc(Hons)Eng said...

Art,
Conventional medicine has nothing further to offer my mum. I shall be meeting the GP who visits the nursing home tomorrow to discuss my approach with her. Interestingly, the NHS blocks internet access to blogspot.com from hospital PCs. I would like to have found more human trials of Vitamin K2 on mental function.

RE your daughter: Is she trying to gain muscle mass, strength, or a bit of both? There are different optimum rep ranges for muscle hypertrophy vs strength. If she is practicing 4-6 hr/d, she's probably burning a lot of kcals each day. To gain mass, she needs to eat more but not too much more, as women can only gain ~0.25lb of muscle mass a week if they're lucky.

What does the practice involve? Does she do resistance training with weights or machines? Such training requires a relatively high intake of carbohydrate to fuel the training & increase muscle growth. Protein intake needs to be 1-1.5g of protein per lb of LBM.
LBM = Bodyweight(1-(Bodyfat%/100))

Dr. Art Ayers said...

Nigel,
Thanks for the guidance. She needs to gain strength, burst speed and stamina, but she is also a little lean to survive the 5am work outs on the lake at 10C. She does mostly whole body erg/rowing machines for dry land. I just don't think that she eats enough calories. Should she consider protein supplements?
She rows stroke and is trying to move up to the second varsity 8. Her violin background gives her absolute strokes per minute. Very cool.

With your mum, my experience is to get older people back to their prior capabilities ASAP. I think that the cytokine data indicates that older people should be able to regain muscle mass quickly until they have enough muscle activity to lower inflammation. So make sure that the nursing home staff know that you expect your mum to stay active and make rapid progress.
Good luck.

TedHutchinson said...

Dr. McCleary's Blog

this has very useful science based information by a brain surgeon on using nutrition to preserve brain function.

TedHutchinson said...

Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract
Michael Zasloff

It was after reading this I realised why I no longer had UTI's regularly. After I had to selfcatheterize 5 times daily repeat UTI's became a real pain, they make you feel so ill and down. I was on a permanent low dose antibiotic as well but I've not taken that for a couple of years now.
Have you had her 25(OH)D checked?
Do you know there's a $30 simple finger prick postal 25(OH)D from
GrassrootshealthDaction

.

Dr. Art Ayers said...

Nigel,
Ted's reference on innate immunity based on antimicrobial peptides and proteins, e.g. lactoferrin, is closely related to my work on inflammation and heparan sulfate proteoglycan (HSPG) metabolism. Note that all of the defensive peptides and proteins have well developed heparin-binding domain consisting of lots of basic amino acids. Bacteria bind to the epithelial cells via the HSPGs on the surface. Mast cell secrete heparin (along with histamine) to block pathogen binding to the epithelium. That is why heparin is harvested from intestines and lungs of cattle or hogs.

The point of interest here is that inflammation shuts down HSPG production and that is why for example, chronic inflammation leads to proteinuria as the kidneys lose their protein barrier = HSPG. Chronic inflammation can also minimize retention of the antimicrobial peptides and proteins as surface HSPG declines.

Was there a lapse in your mum's vitamin D before the UTI? She could have been sailing along on the perfect combination of nutritional supplements to provide unusually good inflammation protection based on all of your efforts and then something happened and a complex inflammatory cascade led to her problems.

I hope she continues to return to health.

Nigel Kinbrum BSc(Hons)Eng said...

Hi all. I don't believe that there was a lapse in mum's D3 intake before the UTI as the level of caps in the bottle was definitely going down.

In mid-December '08, she fainted at a party after over-eating and had an involuntary bowel movement. This is possibly what led to the UTI.

As mum fractured her pelvis in a fall just before admission to hospital, this will delay her getting back to full mobility as she can't walk for long.


Art. RE Your daughter:
To increase stamina, she needs to do low-intensity exercise for long periods (e.g. rowing), which she is already doing.
To stimulate muscle growth, she needs to eat more and do resistance training (with weights or machines) at 80-85% of maximum load for 5-8 reps.
To increase strength, she needs to do resistance training at 90-100% of maximum load for 1-2 reps.

Regarding supplements: If your daughter can't eat 1-1.5g of protein per lb of LBM, protein powder supps will help. Whey powder is useful just after workouts as the branched-chain amino acids don't stay in the stomach for long and increase serum AAs quite quickly. For bulking, 50g of whey is usually accompanied by 50g of dextrose/maltodextrin (to replenish muscle glycogen quickly as more glycogen = more growth). Dextrose is sweet and can cause nausea as it has high osmolarity. Maltodextrin is not sweet and has low osmolarity, so a mixture of the two is usually the most palatable.

At other times, slower-digesting proteins (e.g. meats, poultry, fish, eggs, cheese etc.) are better, to provide a sustained increase in serum AAs. Casein powder is available but it doesn't mix with fluids well or taste particularly pleasant.

See Lyle McDonald's articles.

Angela said...
This comment has been removed by the author.
Dr. Art Ayers said...

Nigel,
It has been a long while since you have blogged. Are you and your mum OK?

Nigel Kinbrum BSc(Hons)Eng said...

Hi Art. Thanks for asking. I've not been in the mood to blog recently as mum's mental state has not improved sufficiently for her to return home (& it looks like it never will) and her health is also slowly deteriorating.

She began to chew pills instead of swallowing them and as a result refused to take the larger ones e.g. Turmeric, Berberine & Glucosamine.

Changing the subject, how's your daughter getting on?

Dr. Art Ayers said...

Nigel,
She took your suggestions and moved up to the second varsity eight. Her team is likely to go to Nationals. She was voted most improved rower of the year and has her name on the plaque!

Sorry about your mum.
Art

TedHutchinson said...

The Alzheimer's ProjectFor people new to Alzheimer's who come across this thread there is a very useful set of video's here and some links to some excellent resources.
Do be aware that this set of videos represents "official" understandings of Alzheimer's and does not therefore include the role of Vitamin D3 in detoxifying the brain nor does it reflect the knowledge we have on
Ketones and Alzheimer's

Nigel Kinbrum BSc(Hons)Eng said...

Thanks for that Ted. As I have no control over the food that mum gets in the nursing home (other than being able to specify vegetarian, diabetic, Kosher etc if necessary), there's zero chance of trying her on a ketogenic diet.

She's continuing to take the D3, K2 & fish oil as the first 2 are small and the fish oil caps can be chewed.

Rosso said...

Hiya Nige,

Very sorry about your mother’s health mate. If the pills are a problem for her (they kind of became annoying for me) you might want to have a look at my current protocol (links clickable):

Omega 3 - comes with a small plastic measure cup
Vitamin K2Vitamin D32 months supply of omega 3 at 5ml per day. So that’s 6 X D3 caps + 8 X K2 caps to give:

2100 mcg K2 per 5ml
5000 iu D3 per 5ml
1058 mg EPA/DHA per 5ml (I’m also taking some Zipvit fish oil caps)
From the Weston A. Price website:

The assimilation and utilization of vitamin D is influenced by the kinds of fats we consume. Increasing levels of both polyunsaturated and monounsaturated fatty acids in the diet decrease the binding of vitamin D to D-binding proteins. Saturated fats, the kind found in butter, tallow and coconut oil, do not have this effect. Nor do the omega-3 fats. D-binding proteins are key to local and peripheral actions of vitamin D.

Nigel Kinbrum BSc(Hons)Eng said...

Hi Rosso. Long time, no see.

Ironically, it's the Omega-3, K2 & D3 that mum doesn't mind taking, though she insists on chewing & popping the fish oil caps no matter how many times I tell her to just swallow them. They are from Nature's Best so maybe the contents of the capsules don't taste too bad.

caseytoussaint said...

During a recent trip to the US (I live in France) I developed UTI for the first time in my life. Unsure of how to get medical help, and reluctant to spend a day at a clinic, I floowed some advice I'd read on the internet to drink baking soda (because of it's effect on pH) - it was miraculous. By then end of the day all symptoms were gone, and they never came back.

Doug said...

A new study just came out showing that women women with too much visceral abdominal body-fat are twice as likely to contract dementia.

My post about the study - http://www.healthhabits.ca/2009/11/25/belly-fat-doubles-your-risk-of-dementia/

Study abstract - http://www.neurology.org/cgi/content/abstract/73/19/1559

Nigel Kinbrum BSc(Hons)Eng said...

Hi Doug.

In my mum's case it wasn't excess abdo fat that caused her dementia. Dementia runs in her family. Her mum (skinny) had it and her sister (skinny) has it. Mum's quite skinny as well. Thanks for the link anyway.

Cheers, Nige.