How many working brain cells do drug company lackeys have?

In Elvis lives!, I referred to the study Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study*, which came to the conclusion:

"Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD."

I then pointed out the following teensy-weensy flaw in the conclusion:

"What the abstract failed to mention was the fact that there were 26 more deaths in the 80mg Atorvastatin group than in the 10mg group. What's worse? Having a major cardiovascular event or being dead?"

On a Mean Forum far away, I pointed out this teensy-weensy flaw in the conclusion and was told "are you really that retarded?" Funnily enough, I never got an answer from that person as to how the conclusion in red was justified by the data in green. I helpfully suggested that it might have something to do with the fact that Atorvastatin 80mg is a 700% increase in sales compared to Atorvastatin 10mg.

I then received an e-mail from Pfizer ® Customer Service with a spoofed sending address (it was fairly obvious that it was spoofed as it was my e-mail address!). There was the usual helpful Outlook Express "Some pictures have been blocked to help prevent the sender from identifying your computer. Click here to download pictures" message. I didn't click. Well, would you? I deleted the e-mail. I've now enabled comment moderation just in case this 'tard feels like spamming my Blog.

Pfizer manufactures Atorvastatin. Ho-hum!

*Funding for the study was provided by Pfizer Inc., New York, New York. Dr. Shepherd has received consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Oxford Biosensors, Pfizer Inc., and Schering-Plough, and lecture fees from AstraZeneca, Merck, and Schering-Plough. Dr. Kastelein has received consulting fees and lecture fees from Pfizer Inc., AstraZeneca, Merck, and Schering-Plough, and grant support from Pfizer Inc. and AstraZeneca. Dr. Bittner has received consulting fees from CV Therapeutics, Novartis, Pfizer Inc., Abbott, and Reliant, and grant support from Pfizer Inc., Atherogenics, Merck, Kos Pharmaceuticals, Abbott, CV Therapeutics, and the National Institutes of Health. Dr. Deedwania has received consulting fees and lecture fees from Pfizer Inc. and AstraZeneca. Dr. Breazna, Dr. Wilson, and Dr. Zuckerman are all employees of Pfizer Inc. Mr. Dobson is an employee of Envision Pharma Ltd., which was a paid consultant to Pfizer Inc. in connection with the development of the manuscript. Dr. Wenger has received consulting fees from CV Therapeutics, Sanofi-Aventis, Schering-Plough, AstraZeneca, Abbott, Merck, and Pfizer Inc., and grant support from Pfizer Inc., Merck, and the National Heart, Lung, and Blood Institute.

How many working brain cells do researchers have?

Apparently (according to a Japanese study referred to in Am I Missing Something??? ), eating/drinking lots of sugary & starchy carbohydrate causes postprandial hyperglycemia (high blood glucose after meals) in people with type 2 Diabetes. No sh*t, Sherlock! Postprandial hyperglycemia "causes damage to blood vessels, inflammation and oxidation and these cause clogged vessels and heart attacks." I think we're all in agreement that postprandial hyperglycemia is BAD. So, how to tackle this thorny problem? By pharmacological approaches i.e. drug therapies. Like, Duh!
And what is Diabetes-UK's (& the ADA's) dietary advice to people with type 2 Diabetes?
"The actual amount of carbohydrate that the body needs varies depending on your age, weight and activity levels, but it should make up about half of what you eat and drink." & under Ten steps to eating well:
"At each meal include starchy carbohydrate foods
Examples include bread, pasta, chapatis, potatoes, yam, noodles, rice and cereals. The amount of carbohydrate you eat is important to control your blood glucose levels." Like, Duh!


I've been doing a bit of research on methylglyoxal (MG) as a result of reading Methylglyoxal on Atkins... Uh oh! Apparently it's very toxic, therefore ketogenic diets are BAD, mmm-kay? MG causes Insulin Resistance and Advanced Glycation End-products which are both deemed to be undesirable.

Consider this: MG is a glycolysis (conversion of glucose to pyruvate) inhibitor. As MG inhibits glycolysis in cells, uptake of Blood Glucose by cells decreases. Oh, look. Cells have become Insulin Resistant! As uptake of Blood Glucose by cells decreases, Blood Glucose rises. Oh, look. Increased Advanced Glycation End-products! It's bleedin' obvious (to anyone with a sufficient number of working brain cells) that, on a high-carb diet, MG is toxic. It's a no-brainer that MG's toxicity disappears on a low-carb/keto diet, when you actually want cells to burn fatty acids/ketones rather than glucose. Like, Duh!

In fact, strangulating the glucose pathway in cells may have benefits. See Cancer.


Here's another one. According to Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet (KD), "The KD resulted in progressive loss of BMC." And yet, just above, "Growth and bone health status were suboptimal as were serum 25-OHD concentrations and dietary intake of calcium and vitamin D." Like, Duh!

Why Most Published Research Findings Are False.

Following on from The future: I just saw it, I thought you might find this 2005 study by John P. A. Ioannidis of interest.

"Summary

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research."

For more on this, see Who pays the piper and Who pays the piper part 2.

Some more nails for the coffin of the "healthy low-fat" diet.

Every time someone writes "I'm eating a healthy low-fat diet", I cringe. It's presumptuous to assume that, because the fat content is low, the diet is automatically healthy. The media tell us it's healthy. The government tells us it's healthy. "Experts" tell us it's healthy. It must be healthy, right? Um...

See After-eating effects: Carbohydrates vs. fats and Reduced oxidation of dietary fat after a short term high-carbohydrate diet.

The low-fat diet was white bread, potatoes, tuna, chicken, carrots, canned fruit, fruit juices, cola, jam, marmalade, sweets, and sugar cubes.

The higher-fat diet was less of the above, plus a fat spread, which consisted of a mixture of lard, palm oil, olive oil, and corn oil (the ratio of polyunsaturated to saturated fat was 0.5:1).

Please excuse the following "shouting", but some facts need to be shouted from the rooftops:-

1) LDL CHOLESTEROL (LDL-C) DOES NOT CLOG YOUR ARTERIES. LDL-C IS NOT BAD CHOLESTEROL.

2) OXIDISED LDL-C (OX-LDL-C) DOES CLOG YOUR ARTERIES. OX-LDL-C IS BAD CHOLESTEROL.

3) LARGE, FLUFFY (PHENOTYPE A) LDL-C OXIDISES SLOWLY.

4) SMALL, DENSE (PHENOTYPE B) LDL-C OXIDISES RAPIDLY.

5) AS THE PERCENTAGE OF CALORIES FROM FAT DECREASES, YOU GET LESS PHENOTYPE A AND MORE PHENOTYPE B.

If you don't believe me (and why should you?), see A very-low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins, with particular reference to the following figure:-

At 50% fat intake, ~15% of the subjects have phenotype B. At 20% fat intake, ~50% of the subjects have phenotype B. At 10% fat intake, over 60% of the subjects have phenotype B. The subjects were all men, but women are no different in this respect.

And now we have Dietary fat intake and subsequent weight change in adults: results from the European Prospective Investigation into Cancer and Nutrition cohorts.

"Results:...The difference in mean annual weight change was 0.90 g/y (95% CI: –0.54, 2.34 g/y) for men and –1.30g/y (95% CI: –3.70, 1.11 g/y) for women per 1 g/d energy-adjusted fat intake (residual method).

Conclusions: We found no significant association between the amount or type of dietary fat and subsequent weight change in this large prospective study. These findings do not support the use of low-fat diets to prevent weight gain."

Note: -1.30g/y means that as dietary fat intake increased, weight decreased.

Look after your brain, Part 2.

Mum used to use a transdermal Natural Progesterone Cream (to reverse hair loss) but she stopped using it some time before she became mentally impaired. I found a half-full pot of the stuff in mum's house and have instructed the nursing staff to rub a blob of cream on mum's skin each day to see if it makes any improvement to her Lewy Body Dementia. See Regeneration in a degenerating brain: potential of allopregnanolone as a neuroregenerative agent , Regenerative potential of allopregnanolone and Progesterone receptors: form and function in brain.

Getting mum to eat more smoked salmon has definitely perked her up. I've also managed to re-introduce turmeric into her diet (she was spitting out the turmeric pills as they were large & unchewable) by getting the nursing staff to stir a teaspoonful of turmeric powder into her orange juice (I & she can't taste it) once every few days. Luckily, she never had any problems taking the Vitamin D3 & K2 capsules/gelcaps.

Finally, I'm trying to get mum on low dose Aspirin, as Aspirin inhibits the aggregation of proteins (synuclein, beta amyloid) on charged polymers in amyloid diseases, such as Parkinson’s disease, Alzheimer’s disease, etc., according to Dr Art Ayers. As mum has a hiatus hernia, which causes acid reflux, her GP may not allow her to do this even though mum is taking a Proton Pump Inhibitor and Gaviscon. See The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer's disease and Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease.

Continued on Look after your brain, Part 3.

Guess who didn't look after his brain?

Due to the sudden deterioration in my mum's physical & mental health and also due to struggling to come to terms with her having to spend the rest of her life in a nursing home (not the happiest of places), my diet went completely to pot.

I "went off" salmon, sardines & powdered linseeds and started to eat carbohydrate/fat-based comfort foods. A black cloud slowly descended over me. I lost the motivation to do anything, including updating this blog. I also slept a lot. This continued for several months.

Then, for no apparent reason, a few weeks ago I got an urge to eat smoked salmon. I added 200g of smoked salmon twice a week back into my diet and after a few weeks, the black cloud started to lift.

Before I started supplementing with Vitamin D3, I used to eat lots of oily fish but did not function correctly mentally. This time, my Vitamin D3 status was good (I never stopped taking supplements even when I had the black cloud over me) but my EPA (Eicosapentaenoic Acid) and DHA (Docosahexaenoic Acid) intakes were near zero.

In conclusion, it would appear that my brain needs adequate Vitamin D3 and EPA and DHA (and magnesium) to function correctly.

I won't be blogging as much as I have been previously, as I've now dumped the vast majority of the nutritional knowledge within my brain into this blog. If I come across anything new, I'll post it here.

Finally, I've found the cheapest source yet of 5,000iu Vitamin D3 gelcaps.

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. Why does the brain contain Vitamin D receptors?

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 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 pufas have benefits. See
Low Plasma N-3 Fatty Acids and Dementia in Older Persons: The InCHIANTI Study and
Disruption of glial (oligodendrocyte and astrocyte) cellular function leads to carnosine (b-alanyl-L-histidine) synthesis failure, and nutrient and protective factor deficiency in neurons with secondary development of oxidative stress and amyloid toxicity, with subsequent neuronal dysfunction and development of dementia which stated "Measures which reduce toxicity to vascular endothelium and glia, such as fish oil, may have potential for reducing the likelihood of development of the disease..."

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 worsen with 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 ,
Vitamin K and sphingolipid metabolism: evidence to date ,
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 and
Natural approaches to prevention and treatment of infections of the lower urinary tract

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.