Monday, March 2, 2009

Dr.Mao, Brain Foods, Autism, And Alzheimer's Prevention

I like Dr. Mao for his quickie Yahoo tidbits... His advice is great! And very aligned to TrackYourPlaque and longevity as well. Sometimes I wonder what's more important...our brain or our heart? Or the vasculature which is what we 'track' at TYP...? I'm grateful actually that ALL in fact improve exponentially with the same program.

How w o n d e r f u l can life be?!?

G-radio:Mraz 'Wonderful Life' *wink*

All the foods and nutrients listed below are inherent ingredients to our TYP heart reversal stories, "essential amino acids, omega oils, minerals and vitamins":
--Taurine from wild seafood and grassfed meat (not found in veggies)
--Arginine
--Other proteins: Leucine, BCAA, L-Carnitine, etc
--Omega-3 fatty acids: EPA DHA (grassfed meat, seafood); ALA (almonds, flax)
--Omega-6 fatty acids: GLA (sesame oil, borage, primrose, hemp)
--Minerals: Magnesium, Iodine, Selenium, Zinc, Boron, Sulfur, etc
--Vitamins: Vitamin D (calcidiol), Vitamin A, Vitamin E (tocotrienols), Vitamin K1 K2 (esp MK7), methylated folic acid, B-vitamins, Niacin (B3), B6/B12/folate/TMG (homocysteine control), acetylated a-Lipoic Acid, etc
--Antioxidant Flavanoids: blueberries, green tea, pycnogenol, red wine, bilberry, et cetera


8 Foods to Keep Your Brain Young and Healthy

By Dr. Maoshing Ni - Posted on Mon, Aug 11, 2008, 1:42 pm PDT
Senility, Alzheimer's, and age-related memory loss: these conditions of mental decline that come with aging can be delayed or even prevented. Besides engaging in daily activities that work out your brain, a regular and balanced diet rich with essential amino acids, omega oils, minerals and vitamins will ensure a vibrant and sharp memory. Eat these foods to give your brain the nutrition it needs.

1. Fish
Protein, an important component in the making of neurotransmitters, is essential to improve mental performance. Aside from being an excellent source of high quality protein, fish are packed with essential oils, such as Omega-3, which protect the brain and supports its development and functioning. Deep sea fish have the highest amounts of fatty acids, and they include salmon, sea bass, halibut, mackerel, and sardines.

2. Blueberries
These delicious berries are full of powerful
antioxidants, which eliminate free-radical damage that causes aging, and they also possess neuroprotective properties that can delay the onset of age-related memory loss by guarding brain cells from damage caused by chemicals, plaque, or trauma. And they combat inflammation, the other factor in aging. 3. Nuts and SeedsNuts and seeds are wonder foods for your brain. Packed with protein and essential fatty acids, nuts and seeds are also chock full of the amino arginine, which stimulates the pituitary gland at the base of the brain to release growth hormone, a substance that declines quickly after age 35; this is a real anti-aging boon to your brain! Whip up a batch of my "Anti-aging brain mix" to bring with you anywhere and eat a small handful in between meals as a daily snack. It will nourish and support your brain. Pack in sealed container or zip-lock bag to preserve freshness.
1 cup walnut
1/2 cup pine nuts
1/4 cup sesame seeds
1/2 cup pumpkin seeds
1/3 cup of dried goji berries (also known as lycium berry, and easily found in health food stores)
1/2 cup dried apricots

4. Cruciferous Vegetables
Broccoli, cauliflower, and Brussels sprouts are all rich in choline, an essential nutrient for memory and brain health. Choline is a precursor to the neurotransmitter acetylcholine, which contributes to healthy and efficient brain processes. As we age, our body's natural choline output declines, and its neurochemical action weakens. You can eat choline-rich foods to increase your production of acetylcholine, which will improve your brain power. Other sources of choline include: eggs, soybeans, peanuts, cabbage, black beans, and kidney beans.

5. Oil: Monounsaturated Fats
Monounsaturated fats contain essential fatty acids and gamma-linolenic acid (GLA), which are crucial for brain development and function, among many other excellent benefits for your health. Olive oil, sesame oil, canola oil, almond oil, flaxseed oil, and fish oil are rich in monounsaturated fats and are good choices for brain health. Population studies show that people with a diet that is high in unsaturated, unhydrogenated fats may have a reduced risk of Alzheimer's disease, whereas those with a diet that is higher in saturated fats and trans fats have an increased risk.

6. L-carnitine Foods
Age-related memory problems are many times caused by plaque buildup and diminished blood supply to the brain, compromising the delivery of nutrients and oxygen. L-carnitine, an amino acid manufactured in your liver, increases circulation in the brain — among a myriad of powerful benefits for your health. Also, because it prevents fat oxidation in the brain, L-carnitine shows some promise in preventing Alzheimer's disease. Good sources of L-carnitine include: meats, fish, poultry, wheat, avocado, milk, and fermented soybeans.

7. Microalgae
Microalgaes from the ocean and uncontaminated lakes, including blue-green algae, spirulina, chlorella, seaweed, and kelp are easy-to-digest, high protein and high-energy supplements-and contain over a hundred trace minerals! Available in your health food store, microalgae are simple to incorporate into your diet to ensure a good, strong brain function. Look for powders you dissolve in juice or flakes you can sprinkle on your food.

8. Green Tea
Green tea prevents an enzyme found in Alzheimer's disease and is also rich in polyphenols, antioxidants that help prevent premature brain aging. Drink two cups a day to get the brain benefits. To decaf tea, steep for 45 seconds and pour out the water, add fresh hot water to the leaves or tea bag — 95% of caffeine will be eliminated.









Ketogenic Diet for Alzheimer's and other Neuro-degenerative/Vascular Diseases

Why is a ketogenic diet effective for neurodegenerative and vascular diseases (like CAD)? I've wondered this since Atkin's became so popular. I've also wondered why such extreme improvements are noticed short- and long-term with Niacin (Vitamin B3; we use either Slo-Niacin or Niaspan at TYP). This one incredible addition to any heart program evolves dramatic plaque remodelling, heart disease reversal, lipoprotein turn-arounds and large ranges of CAC score regressions. In the HATS trial in post-MI patients, Niacin + simvastatin 40mg/d brought about a 90% reduction in mortality and CAD events in ~3yrs compared with placebo. That is quite dramatic. The results are unheard of for conventional, pharmaceutical-derived therapies. Statin-monotherapy brings about only 20-30% depending on the study...which again as the latest WSJ article summarized...so what? These days when individuals carry belly fat and have elevated insulin, heart attacks and coronary surgical interventions are more de rigueur than NAUGHT... despite statins being placed in the water by health care insurances and people's demands.

What is niacin? Niacin mimics 2 things: starvation (living off your body fat/rearend) and ketosis. Niacin binds the ketone body receptor known as PUMA-G. Ketones are generated under many circumstances for instance:
--first 2 weeks of an infant's life -- baby is living on 60-80% brown fat because momma has not produced enough milk yet (as time is required for those lactative n*pples to so-called 'callous up' -- yeah, men out there that is JUST LIKE running a marathon without bandaids on your b**bies *haaa ah* seriously... bloody...d*mn...fun...)
--starvation (think, Survivorman or Bear)
--intermittent fasting (2-4x/wk 18 to 36 hour fasts)
--12-hour fasts (like for the doctor-ordered cholesterol lab testing)
--physical training beyond 40-60min (eg, sex typically does not count)
--low carb diet
--no carb diet
--moderate to high fat (low carb) diet
--moderate to high protein (low carb) diet
--Paleo + IF (intermittent fasting) + exercise


Don't confuse ketosis with Type 1 diabetes DKA (diabetic ketoacidosis) which is highly fatal. Many doctors and other healthcare professionals do this. It is like comparing normal wear-tear like a shopping cart scratching your car versus a 20-car wreck involving multiple fatalities. Ketosis is in fact normal and part of evolution. Humans and other predators up on the food pyramid of life do it all the time. Ketosis is necessary for survival.

The situation known as DKA occurs because the individual has ZERO insulin. Don't worry -- unless Type 1 or 1.5 (LADA) Diabetes is present, we all make plenty of insulin to 100% prevent this. In fact most people produce far too much insulin which raises blood pressure, causes body fat weight gain, TGs, small dense LDL and other inflammatory markers. Too much insulin also hinders proper muscle development (hard-gainers) with resistance and weight training. (DKA may occur but is VERY very rare in Type 2 diabetes -- unless the person has an infection or sepsis.)




Ketones Fix Our Brain

Altered lipid metabolism in brain injury and disorders.
Adibhatla RM, Hatcher JF.
Subcell Biochem. 2008;49:241-68. Review.
Department of Neurological Surgery, Cardiovascular Research Center, Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI., William S. Middleton Veterans Affairs Hospital, Madison, WI 53792, USA.

Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.
PMID: 18751914










Ketogenic Diet Appears to be Neuroprotective For Alzheimer's

The below authors state that "the Ketogenic diet appears neuroprotective, promoting enhanced mitochondrial function and rescuing adenosine triphosphate production" and suggest the value for broad range applications including not just neurovascular conditions but also cancer. We worry about mitochondrial function at TrackYourPlaque (at least I do anyway :) but many others are getting keen to this disorder). Mitochondria are our little nuclear powerhouses that produce our energy currency, e.g. energy packets known as ATP. Mitochondrial dysfunction is what distinguishes many diseases including how gets mercury/aluminum-toxic/brain-damaged from vaccines in children. Read opinions by Seth Roberts PhD HERE (author of the Shangri-La diet, UCB Psychology professor emeritus). Dr.Roberts shares his insightful thoughts and n=1 experiments on brain function and many other topics, including the benefits of fermentation/probiotics. Many TYP members have tried the SLD (not... 'LSD') and lost significant weight with extra light virgin olive oil. It will be very fascinating to see what conclusions will result from examining probiotics. Short-chain saturated fatty acids (SCSFAs: butyrate, propionate, etc) are binders and activators of PPAR-delta, a potent inflammatory and immunomodulatory switch. SCSFAs are produced by anaerobic fermentation and perhaps may be the ingredients that exert the health and longevity benefits of cheese, natto, stinky tofu, yogurt, etc (Nilssen N dissertation). (interestingly...monounsaturated fatty acids in EVO in fact bind PPAR-delta and other PPAR receptors; ketones=beta-hydroxybutyrate indirectly also activates PPAR-delta).
The ketogenic diet: uses in epilepsy and other neurologic illnesses.
The neuropharmacology of the ketogenic diet.
The ketogenic diet and epilepsy. This therapy has been around 80++ yrs.
Progress in neuroprotective strategies for preventing epilepsy.
From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens.





Neuroprotective and disease-modifying effects of the ketogenic diet.
Hartman AL et al. Behav Pharmacol. 2006 Sep;17(5-6):431-9. Review. Free PDF
Below Excerpt

Alzheimer’s disease
Recent studies have raised the possibility that the ketogenic diet could provide symptomatic benefit and might even be disease modifying in Alzheimer’s disease. Thus, Reger et al. (2004) found that acute administration of medium-chain triglycerides improves memory performance in Alzheimer’s disease patients. Further, the degree of memory improvement was positively correlated with plasma levels of β-hydroxybutyrate produced by oxidation of the medium-chain triglycerides. If β-hydroxybutyrate is responsible for the memory improvement, then the ketogenic diet, which results in elevated β-hydroxybutyrate levels, would also be expected to improve memory function. When a patient is treated for epilepsy with the ketogenic diet, a high carbohydrate meal can rapidly reverse the antiseizure effect of the diet (Huttenlocher, 1976). It is therefore of interest that high carbohydrate intake worsens cognitive performance and behavior in patients with Alzheimer’s disease (Henderson, 2004; Young et al., 2005).

It is also possible that the ketogenic diet could ameliorate Alzheimer’s disease by providing greater amounts of essential fatty acids than normal or high carbohydrate diets (Cunnane et al., 2002; Henderson, 2004). This is because consumption of foods or artificial supplements rich in essential fatty acids may decrease the risk of developing Alzheimer’s disease (Ruitenberg et al., 2001; Barberger-Gateau et al., 2002; Morris et al., 2003a, b)...


Carbohydrate restriction as a protective mechanism

A key aspect of the ketogenic diet is carbohydrate restriction. The role of decreased carbohydrates in neuroprotection has been investigated through the use of 2-deoxy-d-glucose (2-DG), a glucose analog that is not metabolized by glycolysis. Lee et al. (1999) found that administration of 2-DG to adult rats at a nontoxic dose (200 mg/kg) for 7 consecutive days produced dramatic protection against hippocampal damage and functional neurological deficits induced by the seizure-inducing excitotoxin kainate. In addition, 2-DG was protective against glutamate-induced and oxidative stress-induced neuronal death in cell culture. The authors also found that reduced glucose availability induces stress proteins, including GRP78 and HSP70, which they proposed act to suppress ROS production, stabilize intracellular calcium, and maintain mitochondrial function..





Why this approach fixes and protects our brain...Cellular mechanisms underlying the neuroprotective activity of the ketogenic diet:
--Reverses damage on energy metabolism
--Reduced glutamate-mediated toxicity
--Normalization effects on γ-aminobutyric acid systems
--Enhances antioxidant mechanisms
--Protects against programmed cell death
--Carb restriction as a protective mechanism and less ROS






Mitochondrial Dysfunction, Heart Disease, and Autism

The Hannah Poling story is quite frankly riveting. This could have been our child. Or your child. After her 19-month vaccination series, Hannah started developing the signs and symptoms for autism, she stopped interacting with her world. Her father Dr. Jon Poling being an MD/PhD Neurologist is now trying to find solutions for not only his own daughter's recovery but also a whole legion of children of this Pharma vaccine-generation. Apparently Hannah exhibits a mitochondrial dysfunction which may be one of several factors (likely vitamin ADEK deficiency, wheat/gluten intoxication, omega-6 overdose and omega-3/saturated fatty acid insufficiency are all factors as well, imho, I'm not an autism expert yet).
Subpopulation of Mitochondrial Autism -- Autism Vox Blog
Jon S. Poling, MD, PhD (2006) -- Developmental Regression and Mitochondrial Dysfunction in a Child With Autism. Journal of Child Neurology, Vol. 21, No. 2, 170-172.


Interestingly, Heart Disease is implicated on the 'spectrum' of mitochondrial disorders. A statement from the United Mitochondrial Disease Foundation on the connection between mitochondrial disease and autism: “Recent published reports about the potential links between mitochondrial disorders and autism demonstrate the urgent need for more research into mitochondrial disease, a devastating and often fatal illness. Mitochondrial dysfunction has also been implicated in Alzheimer’s Dementia, Parkinson’s disease, Huntington’s disease, Heart Disease and Diabetes." It is not surprising to me. Individuals with heart disease often present themselves or their children with clinical autism or other conditions on the autistic spectrum: ADD, bipolar, major depression, schizophrenia. Perhaps mitochrondrial conditions are in fact woefully underdiagnosed. Aren't we all a little on the spectrum...?? I know I am not... the only one.



We Are Only As Strong as Our Weakest Mitochrondria

Mitochondria reside in all our alive cells (not hair or nails). They provide the energy needed for all energetic, metabolic and cellular processes. Honestly, if your car had no engine or an improperly functioning engine, how far do you think you will drive? Or at all?

Like our weakest link, sick mitochrondria bring us down.

How do we keep mitochrondria happy? Provide it the fuels it prefers. Give it the parts that need to be replaced upon damage/use. Don't throw cogs in its machinery.
--Fatty acids (mono-, saturated-, omega-3 long chained pufa, short-chained-saturated, medium- chained-saturated-, etc)
--Proteins
--Complex carbs (eg, vegetables)
--Coenzyme Q10 (involved in very last stop of ATP production)
--Alpha lipoic acid, Carnitine
--Vitamin D (incorporated in the phospholipid membranes and prevents lipid peroxidation)
--Avoid toxins: wheat/gluten/grains/x-s-fruit-fructose/legumes/lectins (which GLOM on and/or generate mitochrondria-auto-antibodies), heavy metals (lead, mercury, aluminum, etc), pesticides, synthetic hormones/horsey-hormones/progestins, drugs/pharmaceuticals (eg, statins for MANY), bisphenol, plastics, acrylate (used in enteric-coating of pharmaceuticals, e.g. Costco 'high potency' fish oil)

6 comments:

Jake said...

What do you think of regularly taking MCT Oil?

Dr. B G said...

Jake,

You know I love MCT oil. It's the 2nd oil next to fish oil (ok, maybe flax is tied for 2nd right now).

There was only one study where MCT oil produced a negative result in animals (mice?). When a 'cocktail' of cortisone and insulin (I? think) were injected along with infusions of MCT oil. Higher blood glucoses were the result, contrary to other positive studies on weight loss, body fat recomposition and lean muscle gains. I've only observed one situation where someone had harder to control diabetes -- a high stress case, hormone imbalances and chronic pain (high insulin state).

Dr. Larry McCleary, retired pediatric neurosurgeon (and wrote the foreword for Dr. Mike/Protein Power) advises a couple of things to control insulin, the mind, hot flushes, migraines and epilepsy... guess what? MCT oil -- and a low carb diet (among some other things) in his book Brain Trust. Haven't read it but it sounds great.

Pharmacologically, MCT oil is derived from coconut oil (the NOW brand is tasteless -- I use 1-3 Tbs when I remember prn) and is a medium-chain saturated fatty acid (Caproic acid, Caprylic acid, and Capric acid contain 6-, 8-, and 10-carbon chains) binding PPAR-delta alpha and gamma... and makes a great skin softener topically :) and many cosmetic companies have figured it out.

Might smooth out wrinkles... :)
in addition to reversing coronary calcifications by raising HDL-2 and 2b and other potential mechanisms.

Let me know how it works if you try it out!

-G

David said...

This is a great post. I had Lyme disease for years. The neuroborreliosis that results from the infection causes a lot of inflammation in the brain, and, untreated, can lead to an Alzheimer's-like condition. Along with an aggressive treatment, I also adopted a ketogenic diet. It was FANTASTIC. I felt so good. I was eating probably 1/2 cup of coconut oil every day (almost every night I mixed almond butter, coconut oil, heavy cream, roasted/salted sunflower seeds (I made them myself-- with coconut oil), coconut shreds, and stevia together into a disgusting looking, but very tasty and filling snack).

I ate a lot of animal fat, a lot of butter, a lot of meat, and quite a bit of cheese. Eventually I had to start eating fruit (apples and pears were almost all I had in that department) to keep from losing too much weight. I dropped down to 125 from 160 lbs in a few months. I looked kind of like a holocaust victim, but I felt terrific!!

Dr. B G said...

David,

WOW -- that is wonderful to hear how you've recovered after such a horrific infection that is not easy at ALL to beat. (Now you know why I have an AVERSION to ticks :) and for some reason they like to jump all over me *ick*)

Saturated fatty acids really provide more than just some degree of saturation and structure to the human mammalian system. It has anti-bacterial/fungal/viral properties too. It is so interesting that you bring up cocount oil too! My sister 'M' is just ADDICTED and OBSESSED with it right now. I started add it to my morning coffee and eating it straight out of the can. I feel a little more energetic (or it's just the strong French-pressed premium diesel I drink)! She can't stand the coconut 'butter' which tastes nasty to her -- so I've got all her stuff now.

An interesting story someone told me about their father with Alzheimers triggered this blog. The family had to send him back to Calif from Florida, so they diapered him up and gave him only a liquid diet (eg, semi-low carb, low calorie) for the airplane travel. Guess what happened? To the family, they noticed he had more lucidity and even some short-term memory returned. The junk that is fed at most Alz adult-day cares is horrid -- and feeds this condition beyond repair. Like our current SAD too.

-G

Anna said...

G,

Do you know anything about dietary interventions for Rhett Syndrome? I have an acquaintance with a daughter with RS. She's tube fed for the most part and confined to a wheel chair, plus she takes various medications for seizures, GI symptoms, etc., maybe even metformin (my memory is hazy on this). The second ingredient in the liquid meal replacement is sugar, of course.

About a year ago we were talking and I told her about my recnet awareness of MCT oil, its benefits for the brain, and Dr. McLeary, etc. and suggested she might want to review some info and ask the doctor about it. Of course, the doctor wasn't encouraging, but also didn't say there was a good reason not to supplement with MCT oil, so she did.

About 5 months later I saw her again and she said there had been noticeable improvements in her daughter. I don't remember specifically what the improvements were, other than weight gain (which is a good thing for this undersized child), but I think there may have been cognitive improvements, too. Clearly, it isn't going to cure her, but still, gotta wonder what benefits MCT could have provided if administered years ago. Yet, the doctor still wasn't at all interested in the MCT oil.

I saw the mom again last week and she continues to be enthused about the MCT oil and also said another practitioner who sees her daughter (maybe a dietician, PT, or the gastroenterologist?) was now suggesting MCT oil for some other patients. They are now considering a ketogenic diet for the girl, too.

This mom is really up on much of the research on RS, but the diet stuff isn't really well researched at all, so I figured a creative mind like yours might have some ideas.

Dr. B G said...

Hi Anna,

I'm sorry to hear about your friend's daughter. Did you mean Rett Syndrome?

Unfortunately, this is the first that I've heard regarding this condition but many conditions maybe inter-related I'm finding in regards to the root source of the problem -- alterable v. unalterable nutritional exposures and deficiencies in utero or during developement (best example, in utero/childhood grain-exposure leading to narrow dental arches, etc).


Rett's Syndrome (RS) is apparently related to 'Mutations in methyl DNA binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome' (Hansen JC.
Biochem Cell Biol. 2009 Feb;87(1):219-27.).

Are there any foods, antioxidants, co-factors, supplements that may increase the binding between DNA???

At TYP many people take the activated already methylated forms of folic acid. Betaine was studied with no benefit in young RS patients, but perhaps other activated folate forms may be more effective? folinic acid? TMG (trimethyl glycine)? et cetera?

I think n=1 is always a worthwhile experiement given the untenable options with conventional RS treatment...

Emma has talked about folate and perhaps its induction of asthma in children of mothers who take supplement folate. I think she has some very curious theories about in utero exposure and definitely worth examining more closely.
http://blog.plantpoisonsandrottenstuff.info/

The researcher Hartman from John Hopkins also believes a ketogenic diet, as you wonderfully and amazingly already concluded, would be beneficial for all seizure syndromes, incl the genetic ones like RS.

I'd love to hear how it works out.

Good luck and Anna and so nice hearing from you!
G


Epilepsia. 2008 Nov;49 Suppl 8:53-6.

Does the effectiveness of the ketogenic diet in different epilepsies yield insights into its mechanisms?
Hartman AL.
Pediatric Epilepsy Center, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
ahartma2@jhmi.edu

The ketogenic diet (KD) has been used successfully in a variety of epilepsy syndromes. This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. It also includes syndromes where genetics play a major role, such as Dravet syndrome, tuberous sclerosis, and Rett syndrome. Study of the KD in humans and animals harboring various genetic mutations may yield insights into the diet's mechanisms. Comparison of the diet's effectiveness with other treatments in specific syndromes may be another useful tool for mechanistic studies. The diet's utility in epilepsy syndromes of various etiologies and in some neurodegenerative disorders suggests it may have multiple mechanisms of action.
PMID: 19049588




Am J Clin Nutr. 2009 Mar 4.
Epigenetic mechanisms for nutrition determinants of later health outcomes.
Zeisel SH.
Epigenetic marking on genes can determine whether or not genes are expressed. Epigenetic regulation is mediated by the addition of methyl groups to DNA cytosine bases, of methyl and acetyl groups to proteins (histones) around which DNA is wrapped, and by small interfering RNA molecules. Some components of epigenetic regulation have evolved to permit control of whether maternal or paternal genes are expressed. The epigenetic imprinting of IGF2 expression is an example of maternal and paternal epigenetic marking that modulates fetal growth and fetal size. However, epigenetic regulation also permits the fetus and the infant to adapt gene expression to the environment in which it is growing; sometimes when this adjustment goes awry, the risk of chronic disease is increased. Recent progress in the understanding of nutritional influences on epigenetics suggests that nutrients that are part of methyl-group metabolism can significantly influence epigenetics. During critical periods in development, dietary methyl-group intake (choline, methionine, and folate) can alter DNA and histone methylation, which results in lifelong changes in gene expression. In rodent models, pregnant dams that were fed diets high in methionine, folic acid, and choline produced offspring with different coat colors or with kinked tails. A number of syndromes in humans can be caused by defective epigenetic regulation, including Rett syndrome. There are interesting examples of the effects of nutrition in early life that result in altered health in adults, and some of these could be the result of altered epigenetic regulation of gene expression.
PMID: 19261726