Category Archives: Diets - Page 2

Ketogenic Diet for NBIA (Neurodegeneration with Brain Iron Accumulation)

Posted by on February 22, 2011 63 comments

It’s always a pleasure to hear from readers who report improved health.

Some of these emails are poignant: distressing because of the pain of their diseases, yet heartening because of the improvements a good diet brings.

It can’t get more poignant than to hear that children with a painful, deadly, and untreatable disease have, thanks to diet, begun smiling, laughing, and getting better.

Last week Kindy Flyvholm, who bought our pre-publication e-book, wrote with just such a report. I’m delighted to be able to pass it on, and hopeful that this report will help other children escape unnecessary suffering and enjoy life more abundantly. Thank you, Kindy, for sharing your story!

Ketogenic diets as therapy for neurological dysfunction

In our book and on this blog, we advise everyone with a neurological or brain disorder to try a ketogenic (“ketone generating”) diet. The book spells out how to tweak the Perfect Health Diet to make it ketogenic: basically, reduce carbs and add copious amounts of coconut oil.

Ketogenic diets can be surprisingly helpful with brain and nerve dysfunctions. The reason is that neurons have very limited metabolic options: they can burn only glucose or ketones. Glucose metabolism is complex and prone to failure; ketone metabolism is simple and robust. Especially in disease states, a neuron on glucose can be a totally different creature from a neuron on ketones. Neurological diseases that are disastrous on a glucose-rich diet can become mild when neurons are fed ketones.

It doesn’t work for every brain disease, in part because ketones don’t diffuse through the brain all that well. Ketones reach the subcortical and inner cortical layers of the brain easily, but don’t readily reach superficial layers. [1] However, in some diseases the places reached by ketones are the ones in trouble. The evolutionarily oldest parts of the brain, such as the brain stem, are the most likely to benefit from a ketogenic diet. Thus, neurodegenerative diseases that cripple the body may be top candidates for a therapeutic ketogenic diet.

NBIA (Neurodegeneration with Brain Iron Accumulation)

One such disease is NBIA, short for Neurodegeneration with Brain Iron Accumulation. NBIA is most commonly caused by a mutation in the gene PANK2, which codes for the mitochondrial enzyme that converts vitamin B5 (pantothenic acid) into CoenzymeA (a crucial metabolic substrate). This version of NBIA is called PKAN, for pantothenate kinase-associated neurodegeneration.

NBIA/PKAN is characterized by an accumulation of iron in the basal ganglia of the brain. The iron is readily visible in brain MRIs, producing an “eye of the tiger” brightness pattern. [2] It produces symptoms that overlap with those of Parkinson’s disease. [3] About 1 in 500 people carries a PANK2 mutation, so some form of the disease strikes 1 in 250,000 people.

The disease typically first presents itself about age 3, when leg dystonia and spasticity causes an impaired gait, sometimes including toe-walking. The disease progresses and children lose the ability to walk. Dystonia extends to the hands and the face; the head cannot be held upright, and swallowing becomes difficult. Blindness from retinopathy and hearing loss often develop. Premature death occurs usually in the teens, often by age 10 or younger. The last years are excruciatingly painful.

Here is a picture of Zach, age 12:

You can see his inability to hold his head upright, and the hand position characteristic of dystonia. Zach cannot swallow naturally and has to be tube-fed.

The bumps in his chest are from the battery packs used to drive a deep brain stimulation device. The idea is to introduce signals that counter the excruciatingly painful dystonic spasms. Like other therapies for NBIA, deep brain stimulation is often ineffective. In Zach’s case, the device worked for less than one month. It is now turned off but is not removed because the operation would be too traumatic.

Ketogenic Diet Therapy

Kindy writes:

It was in desperation that we began researching options (ANY OPTION) to prevent the horrible pain that precedes death especially in the case of children with early-onset NBIA.

Many research paths led to the ketogenic diet being an option.  A lot of discouraging information was presented as well (like how impossible it is to follow or how disruptive it is to family life, etc).

It’s remarkable, but doctors are so divorced from dietary science that they do not know how simple and natural a ketogenic diet can be, and assume that only absurdly onerous formulations are needed. As we point out in the book, a large fraction of mammals eat ketogenic diets as their natural diet; and all mammals including humans subsist on ketones during starvation.

Doctors were pessimistic about its chances, but a ketogenic diet produced amazing results:

My son, who is 6, … has been on the diet for less than one month and his hands have relaxed enough for him to regain his pointing ability (which had been lost).

Zach, the 12 year old on the diet, is much further progressed in the disease.  Zach has been on the diet since late October, 2010, reaching 80% fat levels towards mid-December.  The following are the improvements that have been noted by Zach’s family and therapists:  Zach has begun holding up his head even though his neck has been hyper extended backwards since he was 9, he has begun pointing with his finger again instead of the palm of his hand, he is moving his right arm again some, and the latest thing is that he is now able to go from a laying position to a sitting position on his own by hanging on to something or someone.  He has not done this since he was 9 years old.

Both boys have begun smiling and laughing all the time.

I know just how they feel!

The previous picture was Zach before starting the ketogenic diet. Here he is on the diet:

Kindy continues:

Zach has gotten off all pain medicine and only has a small amount of 3 [anti-spasmodic] medicines left which hopefully he can get off of over the next year.

Going in and out of ketosis has immediate effects, as this anecdote shows:

Zach had a recent day where his muscle spasms returned severely.   Bad enough he needed to go to the hospital for morphine.  At the last minute (before going to the hospital), the parent looked at her recipe for that day and realized she had used a lot of white chicken meat.  She added in some more coconut oil into his next few tube feedings and the spasms went away immediately.  This is extremely powerful.

Kindy concludes:

We are not under any delusions.  Our children may be taken from us at any time.  If they are taken pain free, then we are blessed compared to the alternative.  The situation thus far with our ‘experiment’ has proven much more than we could have hoped.

Conclusion

Kindy, it’s wonderful that your research and perseverance has bought hope to your son, and that you’re spreading the word to help others find the same hope. I’m so grateful that you’ve shared your story with us. Hopefully your experiences will reach the NBIA community, save children from unnecessary pain, and maybe extend their lives significantly!

We salute every parent who has to deal with neurological and genetic diseases in their children. As this disease illustrates, anyone with a neurological disorder should experiment with a ketogenic diet. Ketogenic diets have been tested in very few diseases, and there is no telling how many neurological diseases may prove amenable to this therapy. But there is already considerable evidence that neurological diseases of the elderly, such as Alzheimer’s and Parkinson’s, are treatable with a ketogenic diet.

Last Thursday, I defended the idea of a healthy diet as the best therapy for disease (“Therapy AND Life”). The NBIA kids illustrate just how powerful dietary therapies can be.

Medical doctors seem to have great misapprehensions and fear of experimenting with this diet. They do not understand it, don’t know how it should be implemented, and have never tried it themselves. Many of the medical ketogenic diets are malnourishing and generate terrible side effects. Not surprisingly, many patients quit the diets.

This coming Thursday, I’ll discuss how to implement a safe, healthy, and pleasurable-to-eat ketogenic diet. There’s no reason for an unpalatable or malnourishing diet to stop patients from enjoying the benefits that Zach has seen!

References

[1] Hawkins RA, Biebuyck JF. Ketone bodies are selectively used by individual brain regions. Science. 1979 Jul 20;205(4403):325-7. http://pmid.us/451608.

[2] Gregory AM, Hayflick SJ. Neurodegeneration with brain Iron Accumulation. Orphanet Encyclopedia, September 2004. http://www.orpha.net/data/patho/GB/uk-NBIA.pdf.

[3] Klein C et al. Hereditary parkinsonism: Parkinson disease look-alikes–an algorithm for clinicians to “PARK” genes and beyond. Mov Disord. 2009 Oct 30;24(14):2042-58. http://pmid.us/19735092. Paisán-Ruiz C et al. Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. Mov Disord. 2010 Sep 15;25(12):1791-800. http://pmid.us/20669327.

Fasting and the Ketogenic Diet for Migraines

Posted by on December 21, 2010 82 comments

We’ve previously argued that people with migraines should try a ketogenic diet. There are two reasons: (1) ketones can evade certain mitochondrial defects which might cause migraines, and (2) ketones reduce glutamate levels, and glutamate toxicity is implicated in migraines.

Reader Rob Sacks has had lifelong migraine headaches. As an experiment he turned to desperate measures – a long fast. Here’s his story:

I fasted for 30 days.   When I say “fast” I mean that I stopped eating all food.   I consumed only water and occasionally sea salt and potassium tablets.

As part of the fast I stopped taking Imitrex which I had been using almost daily to control my migraines.   I did this because I thought Imitrex was increasing the number of migraines due to a rebound effect.   I also stopped consuming caffeine to which I was addicted.

As the fast went on, my migraines lasted for shorter periods of time, and they became less painful. 

By day 23 I became free of headaches.  There was still some sort of migraine activity — I could often feel the sensations that in all my previous life, had always been followed by a headache — but no headache resulted.   Judging from what I could feel, there is a cascade of events that leads to a migraine, and the metabolic changes induced by the fast were interrupting the cascade at a certain point.

I was quite happy with this result and continued the fast as long as I could in the hopes that this would increase the chances that the change would be permanent.

Unfortunately, after the fast ended, the headaches gradually came back. I think this happened because after the first few post-fast meals, I made no effort to keep my diet ketogenic. An intense craving for fruit developed and once the danger of refeeding syndrome seemed to be over, I gave in. This was interesting because before the fast I had been on low carb diets since 2007 and hadn’t craved carbs in years.

When I saw the gains slipping away, I fasted again for two days to get back into ketosis as quickly as possible. Then I started following a diet similar to those used by neurologists at Johns Hopkins to treat children with epilepsy, with calorie restriction, frequent meals, and a ratio of fat to protein (by weight) of four to one. After two days of this diet, my headaches stopped again. That was only 48 hours ago but I’m sure the diet is working because I challenged myself last night with a sure-fire migraine trigger by staying up past my bedtime to watch the eclipse. Normally this would create a debilitating headache, but the only result was a slight migrainy feeling that was easily controlled with two aspirin. Before the fast, aspirin had no apparent effect on my migraines.

The next step will be to try more moderate diets and find the least extreme one that controls the headaches.

The fast proved that migraine headaches can be stopped by the metabolic changes induced by fasting.  Hopefully I can find a way to make that same metabolic state occur permanently.

Incidentally, the fast had some unexpected beneficial effects.  A bad varicose vein is dramatically improved, and a teary eye problem (which I think was caused by a clogged tear duct, and which I previously controlled with large amounts of vitamin C) has resolved almost completely.

I think this kind of experimentation is extremely important. Through experiments like Rob’s we can learn more about the causes of these seemingly incurable health conditions and find dietary and nutritional methods for healing or mitigating them. Experiments in lab mice are important, but the mice don’t tell us what they’re experiencing!

Rob lost 22 pounds during his 30-day fast, equivalent to 2200 calories per day if taken equally from protein and fat. Such an extended loss of lean tissue can be quite dangerous. If he had taken coconut oil or medium chain triglycerides during his fast, he would have conserved lean tissue mass and might have actually increasing ketone availability.

Fortunately it looks like ketogenic dieting is the key to Rob’s migraine relief, so extreme fasting should not be necessary.

Fasting does have therapeutic actions apart from its elevation of ketones. For instance, it promotes autophagy. It is possible that the fasting, not the ketones, was responsible for Rob’s cure of his varicose vein and teary eyes.

Rob might wish to experiment with protein restriction and other techniques for autophagy promotion, in order to see if they might also be beneficial in addition to ketosis.

Also, experimenting with micronutrients is important. Magnesium and riboflavin are often helpful for migraines.

Good luck Rob! Keep us posted.

Dangers of Zero-Carb Diets, IV: Kidney Stones

Posted by on November 23, 2010 123 comments

Kidney stones are a frequent occurrence on the ketogenic diet for epilepsy. [1, 2, 3] About 1 in 20 children on the ketogenic diet develop kidney stones per year, compared with one in several thousand among the general population. [4] On children who follow the ketogenic diet for six years, the incidence of kidney stones is about 25% [5].

A 100-fold odds ratio is hardly ever seen in medicine. There must be some fundamental cause of kidney stones that is dramatically promoted by clinical ketogenic diets.

Just over half of ketogenic diet kidney stones are composed of uric acid and just under half of calcium oxalate mixed with calcium phosphate or uric acid. Among the general public, about 85% of stones are calcium oxalate mixes and about 10% are uric acid.  So, roughly speaking, uric acid kidney stones are 500-fold more frequent on the ketogenic diet and calcium oxalate stones are 50-fold more frequent.

Causes are Poorly Understood

In the nephrology literature, kidney stones are a rather mysterious condition.

Wikipedia has a summary of the reasons offered in the literature for high stone formation on the ketogenic diet [4]:

Kidney stone formation (nephrolithiasis) is associated with the diet for four reasons:

  • Excess calcium in the urine (hypercalciuria) occurs due to increased bone demineralisation with acidosis. Bones are mainly composed of calcium phosphate. The phosphate reacts with the acid, and the calcium is excreted by the kidneys.
  • Hypocitraturia: the urine has an abnormally low concentration of citrate, which normally helps to dissolve free calcium.
  • The urine has a low pH, which stops uric acid from dissolving, leading to crystals that act as a nidus for calcium stone formation.
  • Many institutions traditionally restricted the water intake of patients on the diet to 80% of normal daily needs; this practice is no longer encouraged.

These are not satisfying explanations. The last three factors focus on the solubility of uric acid or calcium in the urine; the first on availability of calcium, one of the most abundant minerals in the body.

There is no consideration of the sources of uric acid, oxalate, or calcium phosphate.

Two of the factors focus on urine acidity, but alkalinizing diets have only a modest effect on stone formation. In the Health Professionals Study and Nurses Health Study I and II, covering about 240,000 health professionals, people with the lowest scores for a DASH-style diet (an alkalinizing diet high in fruits, vegetables, nuts, and legumes) had a kidney stone risk less than double that of those with the highest DASH-style scores. [6]

On ketogenic diets specifically, supplementation with potassium citrate to alkalinize the urine and provide citrate reduced the stone formation rate by a factor of 3. [3] They were still more than 30-fold more frequent than in the general population.

It seems the medical community is still unaware of some primary causes of stone formation.

Uric Acid Production

One difference between a ketogenic (or zero-carb) diet and a normal diet is the high rate of protein metabolism. If both glucose and ketones are generated from protein, then over 150 g protein per day is consumed in gluconeogenesis and ketogenesis. This releases a substantial amount of nitrogen. While urea is the main pathway for nitrogen disposal, uric acid is the excretion pathway for 1% to 3% of nitrogen. [7]

This suggests that ketogenic dieters produce an extra 1 to 3 g/day uric acid from protein metabolism. A normal person excretes about 0.6 g/day. [8]

In addition to kidney stones, excess uric acid production may lead to gout. Some Atkins and low-carb Paleo dieters have contracted gout.

Oxalate Production

Our last post (on scurvy) argued that very low-carb dieters are probably inefficient at recycling vitamin C from its oxidized form, dehydroascorbic acid or DHAA.

If DHAA is not getting recycled into vitamin C, then it is being degraded. Here is its degradation pathway:

The degradation of vitamin C in mammals is initiated by the hydrolysis of dehydroascorbate to 2,3-diketo-l-gulonate, which is spontaneously degraded to oxalate, CO(2) and l-erythrulose. [9]

Oxalate is a waste material that has to be excreted in the kidneys. Vitamin C degradation is a major – in infections, probably the largest – source of oxalate in the kidneys:

Blood oxalate derives from diet, degradation of ascorbate, and production by the liver and erythrocytes. [10]

Since the loss rate from vitamin C degradation can reach 100 g/day in severe infections, and most of that mass is excreted as oxalate, it is apparent that a very low-carb dieter who has active infections, as did I and KM in the scurvy post, or some other oxidizing stress such as injury or cancer, may easily excrete grams of oxalate per day, with the amount limited by vitamin C intake.

Dehydration and Loss of Electrolytes

Excretion of oxalate consumes both electrolytes, primarily salt, and water:

In mammals, oxalate is a terminal metabolite that must be excreted or sequestered. The kidneys are the primary route of excretion and the site of oxalate’s only known function. Oxalate stimulates the uptake of chloride, water, and sodium by the proximal tubule through the exchange of oxalate for sulfate or chloride via the solute carrier SLC26A6. [10]

Salt and water are also needed by the kidneys to excrete urea and uric acid.

Personally, I found that my salt needs increased dramatically on a zero-carb diet. I needed at least a teaspoon per day of salt when zero-carbing, compared to less than a quarter-teaspoon when eating carbs.

As a result of loss of salt and water, low-carb dieters tend to become dehydrated. This is also a widely-observed side effect on ketogenic diets.

We’ve all seen what happens to urine when we’re dehydrated: it becomes colorful due to high concentrations of dissolved compounds.

As urine becomes saturated, it no longer possible for uric acid and oxalate to dissolve. They precipitate out and initial deposits nucleate further deposits to form kidney stones.

Polyunsaturated Fats and Kidney Stones

That brings us to another factor that promotes kidney stones: high omega-3 polyunsaturated fat consumption.

Here’s the data:

Older women (NHS I) in the highest quintile of EPA and DHA intake had a multivariate relative risk of 1.28 (95% confidence interval, 1.04 to 1.56; P for trend = 0.04) of stone formation compared with women in the lowest quintile. [11]

Eating omega-3 fats promotes calcium oxalate kidney stones about as much as eating oxalate. The top quintile of dietary oxalate intake has a relative risk of 1.22. [12]  (The top dietary source of oxalate is spinach, by the way.)

So what about EPA and DHA promotes kidney stone formation?  A clue comes from julianne of Julianne’s Paleo & Zone Nutrition Blog; she made a very interesting comment:

A few years ago I started taking a high dose of Omega 3, because of joint inflammation, and other issues. This made big difference for about 3 months, then seemed to not work any more. I talked to a nutritionist friend and she pointed out that according to Andrew Stoll (The Omega 3 Connection) you must take 1000 mg vit C and 500 iu vit E daily or the omega 3 becomes oxidised in your body (cell membranes) and ineffective. I started taking both and in days was back to the original anti-inflammatory effectiveness of omega 3. I have since talked to others about this – for example a psychiatrist whose clients did well on omega 3 for 3 months and then it became ineffective.

Paleo advice from many is to consume a high dose of omega 3, and at the same time reduce carbs. I am wondering if there are people suffering vit C depletion as a result of increased omega 3 consumption as well as too low carbs?

EPA and DHA have a lot of fragile carbon double bonds – 5 and 6 respectively – and are easily oxidized. It’s quite plausible that this lipid peroxidation can lead to oxidation and degradation of vitamin C.

If so, then higher EPA and DHA consumption would increase the flux of oxalate through the kidneys and raise the risk of calcium oxalate stones. It makes sense that the effect is strongest in the elderly, who tend to have the worst antioxidant status.

What Does This Tell Us About the Cause of Stones in the General Population?

Since most kidney stones afflicting the general public are calcium oxalate stones, it seems likely that vitamin C degradation may be the major source of raw material for kidney stones.

If so, then the risk of kidney stones can be greatly reduced by dietary and nutritional steps.

First, the rate of oxidation can be slowed by higher intake of antioxidants such as:

  • Glutathione and precursors such as N-acetylcysteine;
  • Selenium for glutathione peroxidase;
  • Zinc and copper for superoxide dismutase;
  • Coenzyme Q10 for lipid protection;
  • Alpha lipoid acid;
  • Colorful vegetables and berries.

Vitamin C supplementation has mixed effects: its antioxidant effect is beneficial but its degradation is harmful.

Second, electrolyte and water consumption are important. Salt is especially important.

Finally, alkalinizing compounds like lemon juice or other citrate sources can increase the solubility of uric acid.

Conclusion

Zero-carb dieters are at risk for

  • Excess renal oxalate from failure to recycle vitamin C;
  • Excess renal uric acid from disposal of nitrogen products of gluconeogenesis and ketogenesis;
  • Salt and other electrolyte deficiencies from excretion of oxalate, urea and uric acid; and
  • Dehydration.

These four conditions dramatically elevate the risk of kidney stones.

To remedy these deficiencies, we recommend that everyone who fasts or who follows a zero-carb diet obtain dietary and supplemental antioxidants, eat salt and other electrolytes, and drink lots of water.

Also, unless there is a therapeutic reason to restrict carbohydrates, it is best to obtain about 20% of calories from carbs in order to relieve the need to manufacture glucose and ketones from protein. This will substantially reduce uric acid excretion. If it also reduces vitamin C degradation rates, as we argued in our last post, then it will substantially reduce oxalate excretion as well.

Related Posts

Other posts in this series:

  1. Dangers of Zero-Carb Diets, I: Can There Be a Carbohydrate Deficiency? Nov 10, 2010.
  2. Dangers of Zero-Carb Diets, II: Mucus Deficiency and Gastrointestinal Cancers A Nov 15, 2010.
  3. Danger of Zero-Carb Diets III: Scurvy Nov 20, 2010.

References

[1] Furth SL et al. Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol. 2000 Nov;15(1-2):125-8. http://pmid.us/11095028.

[2] Herzberg GZ et al. Urolithiasis associated with the ketogenic diet. J Pediatr. 1990 Nov;117(5):743-5. http://pmid.us/2231206.

[3] Sampath A et al. Kidney stones and the ketogenic diet: risk factors and prevention. J Child Neurol. 2007 Apr;22(4):375-8. http://pmid.us/17621514.

[4] “Ketogenic diet,” Wikipedia, http://en.wikipedia.org/wiki/Ketogenic_diet.

[5] Groesbeck DK et al. Long-term use of the ketogenic diet. Dev Med Child Neurol. 2006 Dec;48(12):978-81. http://pmid.us/17109786.

[6] Taylor EN et al. DASH-style diet associates with reduced risk for kidney stones. J Am Soc Nephrol. 2009 Oct;20(10):2253-9. http://pmid.us/19679672.

[7] Gutman AB. Significance of uric acid as a nitrogenous waste in vertebrate evolution. Arthritis Rheum. 1965 Oct;8(5):614-26. http://pmid.us/5892984.

[8] Boyle JA et al. Serum uric acid levels in normal pregnancy with observations on the renal excretion of urate in pregnancy. J Clin Pathol. 1966 Sep;19(5):501-3. http://pmid.us/5919366.

[9] Linster CL, Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J. 2007 Jan;274(1):1-22. http://pmid.us/17222174.

[10] Marengo SR, Romani AM. Oxalate in renal stone disease: the terminal metabolite that just won’t go away. Nat Clin Pract Nephrol. 2008 Jul;4(7):368-77. http://pmid.us/18523430.

[11] Taylor EN et al. Fatty acid intake and incident nephrolithiasis. Am J Kidney Dis. 2005 Feb;45(2):267-74. http://pmid.us/15685503.

[12] Taylor EN, Curhan GC. Oxalate intake and the risk for nephrolithiasis. J Am Soc Nephrol. 2007 Jul;18(7):2198-204. http://pmid.us/17538185.

Migraine Sufferers Should Try a Ketogenic Diet

Posted by on September 2, 2010 113 comments

Anyone with an impairment of brain or neurological function – whether mental illness, depression, seizures, brain cancer, headaches, neuropathy, brain infections, or any other neurological condition – should try a ketogenic diet to see if it improves the condition.

 “Ketogenic” means that the diet causes the liver to manufacture ketones. Ketones are small water-soluble compounds that are metabolized like fats. Unlike fats, they do not need carnitine transport to reach mitochondria. They can be used for energy by every mitochondria-containing human cell type. This makes them one of the most disease-resistant sources of dietary energy. There are few things that can go wrong with ketone metabolism.

Ketogenic diets have several major benefits for neurological conditions:

  • They relieve neuronal starvation from cognitive hypoglycemia of any cause.
  • They stimulate the innate immune response against intracellular pathogens, helping to heal brain infections.

Recent work has identified a third benefit from ketogenic diets: They eliminate an excess of glutamate. In a carbon isotope study, feeding the ketone beta-hydroxybutyrate in place of glucose caused less glutamate to be formed in the brain:

The amount of (13)C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4-(13)C]beta-hydroxybutyrate as opposed to [1,6-(13)C]glucose. [1]

This is important because excessive brain glutamate is “excitotoxic” and kills neurons. Glutamate excitotoxicity causes damage in a host of conditions including

spinal cord injury, stroke, traumatic brain injury and neurodegenerative diseases of the central nervous system (CNS) such as multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, alcoholism or alcohol withdrawal and Huntington’s disease. [2]

Other diseases in which damage from glutamate excitotoxicity is important include epilepsy, schizophrenia and various mood and anxiety disorders.

Migraines and Glutamate

My sister’s husband gets frequent migraines, so I keep an eye out for papers about migraines. A new paper in Nature Genetics finds that people with common migraine tend to have a mutation in a regulatory sequence for genes that control glutamate abundance. [3]

People with the mutation are prone to glutamate excitotoxicity:

[A] DNA variation found between the PGCP and MTDH/AEG-1 genes on chromosome 8 appears to be associated with increased susceptibility to common migraine. The variant appears to alter the activity of MTDH/AEG-1 in cells, which regulates the activity of the EAAT2 gene: the EAAT2 protein is responsible for clearing glutamate from brain synapses in the brain….

“Although we knew that the EAAT2 gene has a crucial role to play in neurological processes in human and potentially in the development of migraine, until now, no genetic link has been identified to suggest that glutamate accumulation in the brain could play a role in common migraine,” says co-senior author of the study Professor Christian Kubisch of University of Ulm, Germany (previously at the University of Cologne where he conducted his research for this study.) “This research opens the door for new studies to look in depth at the biology of the disease and how this alteration in particular may exert its effect.” [4]

If glutamate excitotoxicity causes migraines, then it’s likely that migraine sufferers would benefit from a ketogenic diet.

How Do You Eat a Ketogenic Diet?

The safest and healthiest way to eat a ketogenic diet is by:

  • Restricting carbohydrate consumption to 200 calories per day from “safe starches” like rice, taro, and sweet potatoes.  70 grams of cooked white rice, 150 grams of taro, and 300 grams of sweet potato are an appropriate daily ration.
  • Eating massive amounts of coconut oil. The short-chain fats in coconut oil are the most “ketogenic” of foods, i.e. the most readily turned into ketone bodies. 6 to 8 fluid ounces (12 to 14 tablespoons) per day of coconut oil is an appropriate daily ration.

Supplements with vitamin C and selenium should also be increased on a ketogenic diet.

Conclusion

Research on ketogenic diets as a therapy has focused on epilepsy for decades, with some recent interest in using these diets as a therapy for brain cancer. But really, they are likely to be helpful against nearly all brain and neurological conditions, and probably all solid tumor cancers and many infectious diseases as well.

Rather than waiting for the glacial progress of modern biomedical research, which needs decades to assemble sufficient evidence to get an application for funding for a clinical trial past skeptical reviewers, anyone with a brain or neurological condition should simply experiment with a ketogenic diet themselves to see if it helps. Odds are it will.

References

[1] Lund TM et al. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons. J Neurochem. 2009 Jul;110(1):80-91. http://pmid.us/19457063.

[2] Wikipedia, “Excitotoxicity,” http://en.wikipedia.org/wiki/Excitotoxicity.

[3] International Headache Genetics Consortium et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet. 2010 Aug 29. [Epub ahead of print] http://pmid.us/20802479.

[4] “First Genetic Link to Common Migraine Exposed,” Physorg.com, Aug. 29, 2010, http://www.physorg.com/news202139760.html.