Monday, October 30, 2006

Parkinson's Disease

There is a good summary of what to expect from Parkinson's Disease available at the USA based National Parkinson's Foundation website. Briefly, the problem is incurable, progressive and not particularly pleasant. This is the story of a Parkinson's sufferer who was given the possibility of modifying the usual outcome and the pressures which influenced her choice.

Last year, 2005, there was a report in the medical journal Neurology. It described a pilot study of a special diet for the management of Parkinson's Disease. The whole trial only lasted 28 days and only involved seven people, of whom only five completed the full month. In these five there was an improvement in their Parkinson's disease. Keep in mind Parkinson's is supposed to be irreversible... By the way, a small trial like this is VERY significant. If you have a therapy which makes a big difference it will show in a small trial. If your trial needs 100,000 people to show a minor benefit, the benefit for an isolated individual will clearly be pretty well undetectable.

That's interesting in its own right. But much more interesting was the interview with one of the participants published in USA Today. The article tells us what she ate and mentions that she lost 26lb. The study lasted 28 days. That is an impressive weight loss. So what sort of a diet combines modest reversal of an irreversible disease with dramatic weight loss? The diet is what is known as a ketogenic diet. Just a little meat or eggs each day, plus lots and lots of fat. No carbohydrate. Under these conditions the liver manufactures large quantities of ketone bodies, which are an excellent fuel for the brain and easily able to replace at least half of the daily glucose which is usually considered "essential".

It appears that if you feed dopaminergic brain cells on ketone bodies they stop dying, and maybe the sick-but-not-yet-dead ones recover. The brain likes ketone bodies. Why did the weight loss happen? It is self evident that eating fat makes you fat. Just ask any dietician. It's obvious. Very obvious. But not true. Ketogenic diets are excellent for weight loss. The physiology is logical and unimportant here, but minimal carbohydrate intake is essential for it to work.

The USA Today interview finished with the plan for the next phase of the investigation, using a less extreme ketogenic diet. Ketogenic diets are not easy to adhere to. The interviewee had been invited to take part in this next phase but she had refused. That would be fair enough for a minor problem. Having flicked through the description of advanced Parkinson's disease, I personally would want a serious reason to discontinue a diet which might protect me from the ravages described.

What is so wrong with a ketogenic diet that this lady couldn't stand it?

No carrots were allowed.

There is at least one person out there who would rather allow progression of their Parkinson's Disease than give up nice crispy raw carrots.

Carrots. Raw. And pass me the l-dopa please.

Peter

11 comments:

Martin said...

Here's something that shows that at least some people will choose cancer over a carb-free diet.



The women's hospital at the University of Würzburg used to be the biggest of its kind in Germany. Its former size is part of the historical burden it carries — countless women were involuntarily sterilized here when it stood in the geographical center of Nazi Germany.


Today, the capacity of the historical building overlooking the college town, where the baroque and mid-20th-century concrete stand in a jarring mix, has been downsized considerably. And the experiments within its walls are of a very different nature.

Since early 2007, Dr. Melanie Schmidt and biologist Ulrike Kämmerer, both at the Würzburg hospital, have been enrolling cancer patients in a Phase I clinical study of a most unexpected medication: fat. Their trial puts patients on a so-called ketogenic diet, which eliminates almost all carbohydrates, including sugar, and provides energy only from high-quality plant oils, such as hempseed and linseed oil, and protein from soy and animal products.

What sounds like yet another version of the Atkins craze is actually based on scientific evidence that dates back more than 80 years. In 1924, the German Nobel laureate Otto Warburg first published his observations of a common feature he saw in fast-growing tumors: unlike healthy cells, which generate energy by metabolizing sugar in their mitochondria, cancer cells appeared to fuel themselves exclusively through glycolysis, a less-efficient means of creating energy through the fermentation of sugar in the cytoplasm. Warburg believed that this metabolic switch was the primary cause of cancer, a theory that he strove, unsuccessfully, to establish until his death in 1970.

To the two researchers in Würzburg, the theoretical debate about what is now known as the Warburg effect — whether it is the primary cause of cancer or a mere metabolic side effect — is irrelevant. What they believe is that it can be therapeutically exploited. The theory is simple: If most aggressive cancers rely on the fermentation of sugar for growing and dividing, then take away the sugar and they should stop spreading. Meanwhile, normal body and brain cells should be able to handle the sugar starvation; they can switch to generating energy from fatty molecules called ketone bodies — the body's main source of energy on a fat-rich diet — an ability that some or most fast-growing and invasive cancers seem to lack.

The Würzburg trial, funded by the Otzberg, Germany–based diet food company Tavartis, which supplies the researchers with food packages, is still in its early, difficult stages. "One big problem we have," says Schmidt, sitting uncomfortably on a small, wooden chair in the crammed tea kitchen of Kämmerer's lab, "is that we are only allowed to enroll patients who have completely run out of all other therapeutic options." That means that most people in the study are faring very badly to begin with. All have exhausted traditional treatments, such as surgery, radiation and chemo, and even some alternative ones like hyperthermia and autohemotherapy. Patients in the study have pancreatic tumors and aggressive brain tumors called glioblastomas, among other cancers; participants are recruited primarily because their tumors show high glucose metabolism in PET scans.

Four of the patients were so ill, they died within the first week of the study. Others, says Schmidt, dropped out because they found it hard to stick to the no-sweets diet: "We didn't expect this to be such a big problem, but a considerable number of patients left the study because they were unable or unwilling to renounce soft drinks, chocolate and so on."

The good news is that for five patients who were able to endure three months of carb-free eating, the results were positive: the patients stayed alive, their physical condition stabilized or improved and their tumors slowed or stopped growing, or shrunk. These early findings have elicited "very positive reactions and an increased interest from colleagues," Kämmerer says, while cautioning that the results are preliminary and that the study was not designed to test efficacy, but to identify side effects and determine the safety of the diet-based approach. So far, it's impossible to predict whether it will really work. It is already evident that it doesn't always: two patients recently left the study because their tumors kept growing, even though they stuck to the diet.

Past studies, however, offer some hope. The first human experiments with the ketogenic diet were conducted in two children with brain cancer by Case Western Reserve oncologist Linda Nebeling, now with the National Cancer Institute. Both children responded well to the high-fat diet. When Nebeling last got in contact with the patients' parents in 2005, a decade after her study, one of the subjects was still alive and still on a high-fat diet. It would be scientifically unsound to draw general conclusions from her study, says Nebeling, but some experts, such as Boston College's Thomas Seyfried, say it's still a remarkable achievement. Seyfried has long called for clinical trials of low-carb, high-fat diets against cancer, and has been trying to push research in the field with animal studies: His results suggest that mice survive cancers, including brain cancer, much longer when put on high-fat diets, even longer when the diets are also calorie-restricted. "Clinical studies are highly warranted," he says, attributing the lack of human studies to the medical establishment, which he feels is single-minded in its approach to treatment, and opposition from the pharmaceutical industry, which doesn't stand to profit much from a dietetic treatment for cancer.


It seems to me they would have done even better on animal fats, but I suppose there is no chance of funding for that. The last sentence of the item is really quite frightening. Why is it that profit and accurate nutritional information never seem to go together?

Thanks again for the blog.
Day

Peter said...

Hi Martin,

Yes, people would prefer death to giving up sugar.... The study has been discussed in one of the Kwasniewski posts but the one thing which has occurred to me since is that perhaps the cancer patients are pre selected to like sugar. Perhaps that's why they have cancer in the first place. A less sugar driven person might not have ended up in the study in the first place

Hmmm

Peter

PJ said...

Honestly, this doesn't even make sense. You can maintain a full ketogenic diet with more than zero carbs. Most people can have up to about 30, sometimes more depending. You can eat carrots on a ketogenic diet, but since they are high in sugar you just can't eat very many very often. Where did this idea come from that K requires "zero" carbs and that you can never eat carrots again if that's the diet? About the only thing one can't eat again is crap that is horrible for you anyway, like high-sugar/starch produce or grains.

Peter said...

Absolutely. Carrots would be fine on a ketogenic diet, in distinct moderation, but for a crunch fix. They would mostly go down the loo.

I view the carrots as a metaphor for both the need to eat cr@p (that need is intrinsic to being 30kg overweight) because that's what you've always enjoyed, and a metaphor for wanting to conform to society's view of healthy eating. Terminal Parkinsons seems preferable to eating a "funny" diet to some... It just has to be couched in the correct self justifying terminology.

Oh, and it is a press release so any resemblance to reality may actually be accidental.

But she reminds me of the high drop out rate in the German study on ketogenic diets for end stage cancer management. Those with cancer are probably pre selected for liking insulin raising foods.....

Peter

Nigel Kinbrum said...

Note: My mum has Parkinson's Disease and Dementia with Lewy Bodies.

1) I bought a pot of coconut oil to add to her food as this raises serum ketones.

2) Branched chain amino acids maintain ketosis with a lower F:P ratio. Unfortunately...

3) When someone with dementia becomes institutionalised (as mum now is), you lose all control over their diet (Nursing Homes do not have different menus for the mentally-impaired from the physically-impaired) and you cannot give any supplements unless they are first cleared by a Dietician. I am in the process of getting such an appointment.

joyceyjean said...

This hit a nerve. My father passed away from Parkinson's just last year at 72 yo. I can't imagine being willing to go through that devastation if something was shown to slow or reverse it, even if it meant fat and protein only for the rest of my life.

It stole all of his middle age, left him totally debilitated and literally out of his mind (think poo throwing monkeys) at the end. It's disgusting.

He was a great sweet tooth all of his life, yet never weighed more than 125 lbs. and amazingly never diabetic. I'd take both of those over Parkinson's.

Thank goodness for the age of the internet and intelligent, educated bloggers so that I can educate myself and not rely on the PTB.

Peter said...

Hi Nigel, I missed this one first time round, I hope you had some success with the nursing home. I know of one person who managed to get MCTs approved in the UK for dementia and the staff were amazed at the improvement produced, they were used to the minimal effects of pharmaceuticals.

Hi Joyceyjean,

Yes, these things are tragic. I don't think many people realise the cognitive problems involved...

Peter

Eric Thurston said...

Peter,
I've followed your blog for a while now and I have a question for you. In 2008 I was diagnosed with Parkinson's and began researching the disease and possible treatments. I'm taking a pretty standard early dose of carbidopa/levadopa that helped greatly bring my symptoms under control (I was tremoring so badly I would have done anything for relief).

Then, venturing outside the box, I started taking an Ayurvedic herb Kaunch (mucuna pruriens). It helped by smoothing out my peaks and valleys.

After reading the VanItallie study you referenced, I started researching ketogenic diets and especially coconut oil. I'm now on a diet somewhere in the range of 50-55% fat, the rest in roughly equal parts protein and carbs.

As part of this diet I'm taking roughly 4-6 tablespoons of coconut oil per day, like the dose discussed in Mary Newport's blog. The question has to do with whether or how much omega-3 I need to balance the omega-6 in the coconut oil. I've read cautions on several diet blogs about overdoing the fish oil supplements, but I feel that the coconut oil is definitely helping my condition. The dose of the fish oil is 1000 mg per day (one softgel).

Have you ideas about the trade-offs here?

Thanks and I find your blog very informative (and entertaining)

Eric

Peter said...

Hi Eric,

I don't think anyone would worry about 1g/d. I would avoid 100g/d but I took 5g/d for a couple of years and didn't see any obvious benefits or problems. I don't bother nowadays. We eat occasional fish and a ton of UK dairy which always gets grass fed as much as is practical. Grass is cheaper than cattle cake, at least currently, in the UK.

Peter

Matt Huston said...

Sorry for adding to an old thread, but do you have any nutrition - ketosis - Essential Tremor studies or nuggets to share, Peter?

Fascinates me that so many CNS issues have biochemical tie-ins to high-fat and/or ketotic states.

Peter said...

Hi Matt,

I've not looked at essential tremor but I would suspect it's just another facet of the AD/PD/ALS syndrome. Or gluten. Sort of the usual suspects!

Peter