Nutrition and ALS for ALS Awareness Month - Guest Blog

Connections: What are we waiting for?

John Bagnulo MPH, PhD. - Director of Nutrition At Functional Formularies

ALS or amyotrophic lateral sclerosis is a disease centered around the loss of functional mitochondria in motor unit neurons. As these nerve cells lose their ability to generate energy (that’s what mitochondria do) and therefore the ability to stimulate muscle recruitment (required for coordination, movement, and muscle cell preservation), individuals with ALS suffer muscle loss, paralysis, and eventually the ability to swallow and breathe.

Although there is a somewhat broad spectrum of symptoms initially among pALS (people living with ALS), the symptoms most often overlap with other neurodegenerative diseases such as Parkinson’s Disease and Alzheimer’s, as well as with other frontotemporal dementias. While the focus of this article is with respect to the etiology of ALS and the best possible dietary intervention, please keep in mind that the other neurodegenerative diseases also having growing bodies of clinical evidence that illustrate the benefits to a similar dietary pattern.

Neurons are very unique cells. Unlike our muscle cells they are less metabolically flexible and are dependent upon carbohydrates or ketone bodies (more to come on these later...) as fuel sources.Because of their requirements and because of what the modern human diet looks like these days, our brains and the neurons that comprise them are almost always running on sugar. Some sugars are better than others when it comes to the effects on the mitochondria of these critical cells. Glucose burns much more cleanly, for lack of a better analogy, than fructose.

Unfortunately more than half of most sweeteners and added sugars are made up of fructose. When it comes to corn-based sweeteners the percentage can jump to as much as 60% fructose. Many researchers have shown what fructose metabolism does over the course of time to the mitochondria of all cells, it is axiomatic to conclude that it can only be worse in those cells that are even more dependent on sugar metabolism as they will be getting a greaterpercentage of their energy from sugars overall. If this is news to you and you have been told that not only “a calorie is a calorie” but also that “a sugar is a sugar”, you will definitely want to take a look at the research around fructose and mitochondrial dysfunction:

ihttp://www.ncbi.nlm.nih.gov/pubmed/26661172

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529952/pdf/BMR I2015-895961.pdf 

http://www.ncbi.nlm.nih.gov/pubmed/25913123

Simply avoiding fructose is the first and most obvious step in giving our neurons and their mitochondria a chance to come up for air. That means not only avoiding sweeteners but fructose-rich fruits as well. Dried fruits and many fresh ones such as bananas, apples, and grapes are very high in their fructose content and should also be avoided with any neurodegenerative disease. I am always dismayed to find recipes included in dietary recommendations for pALS that are centered on chocolate syrup, ice cream, and numerous other rich sources of sugar. Not only will these recipes fail to prevent weight loss, they will also make ALS patients considerably worse.

The artificial sweetener aspartame is not a good choice either. There is a good amount of research to support the role of glutamic acid in some aspects of the disease. Aspartame contains high concentrations of aspartic acid and it can act and disrupt neuron function in a similar fashion to glutamic acid. Then there is the research illuminating the degeneration of aspartame to methanol and formaldehyde, also potent neurotoxins. Are stevia and xylitol safe sweeteners? Possibly, but they shouldn’t be part of the long- term plan.

The key to arresting the neurodegeneration is in providing the neurons with the only other viable source of energy: ketones. Ketones are generated when we consume small amounts of carbohydrate and moderate amounts of protein. With this type of food consumption, the body has to manufacture glucose in an effort to produce supplemental quantities. In the process, ketones are a byproduct that can benefit all cells in the body with an incredible amount of supporting research. If we eat too many carb- rich foods it will quickly take us out of this ketone-generating zone, as will too much protein.

Ketones can also be generated from certain foods that contain a unique type of fat. In fact, there are only two or three foods that most humans have exposure to at one time or another in their life that can offer ketones as a result of their medium chain triglyceride (MCT) content. Breast milk, goat milk, and coconuts all contain significant amounts of MCTs and therefore can offer ketone production even outside of the ideal parameters of a ketogenic diet.

It makes too much sense that breast milk would provide us with a source of ketones at a time when brain plasticity and development is at its high point. In a similar way it makes too much sense that a ketogenic diet or even a diet rich in extra virgin coconut oil could provide an alternative fuel source to neurons that are otherwise compromised and made worse by their dependency on sugar.

In addition to helping neurons find a more viable source of energy, ketones also signal the cell to initiate autophagy. Autophagy is eventually critical to cellular function. It is a cell’s recycling program where those internal components that are no longer working properly are digested and the proteins and other salvageable components are reinvested into new organelles.

Unfortunately it takes more metabolically extreme circumstances for autophagy to happen. A cell has to receive a signal that there is either a protein or an energy shortage. Ketones are associated with the latter even in the presence of significant quantities of dietary fat. This recycling process creates room in a neuron for new, more functional hardware and can even stimulate biogenesis of new, healthy mitochondria. No drug or medication has ever been able to accomplish that.

This an important foundational component to an ALS, as well as to other neurodegenerative diseases, dietary intervention: get the sugar and the carb bombs out, bring the high quality saturated fats in, most notable extra virgin coconut oil. Even if you are overwhelmed by the thought of a ketogenic diet, simply eliminating sweeteners, fruit juices, most fruits, and other concentrated sources of sugar should be easy to grasp. Replacing omega 6 fatty acid-rich polyunsaturated fats with high quality coconut oil, olive oil, or grass-fed butters is also an extremely worthwhile change. Significant quantities of omega 6 fatty acids generate more inflammation and incorporating more polyunsaturated fats into the mitochondrial membrane just creates more instability and more oxidative stress where it is the most detrimental.

Too often care providers are resistant or unwilling to recommend these high fat, carbohydrate restricted interventions because they are not familiar with the cellular pathways involved in neuron   metabolism. Others confuse this dietary intervention and the mechanisms of ALS with “knowing the cause”. This therapeutic approach does not indicate that there is a proven environmental or genetic cause (although there are certainly some very plausible theories), only that there are definite pathologies in the mitochondria of pALS and that there are ways to improve the metabolic conditions within their neurons. Let’s not wait for another decade to pass before accepting a simple dietary strategy as at least part of the solution. No one should have to wait any longer as the research is becoming increasingly clear.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776126/pd f/fncel-10-00044.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780428/pd f/main.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488864/pd f/1471-2202-7-29.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245363/pd f/nihms320996.pdf

John Bagnulo holds a doctorate in Human Nutrition and Food Science from the University of Maine and a Masters of Public Health from the University of North Carolina. John has served as a nutritionist at Canyon Ranch in the Berkshires, Kripalu Center for Yoga and Health, and is a core faculty member of the Center for Mind-Body Medicine. Additionally he has taught a variety of nutrition and exercise physiology courses at different universities. A frequent lecturer on topics including heart health, detoxification, digestion, and sustainable agriculture, John is also a passionate mountain climber who has reached the top of Mt. Everest as part of a two-man team.

- See more at: http://functionalformularies.com/about/our-team/john-bagnulo#sthash.VpFB5bZR.dpuf

Should the Dying Have the Right to Try Experimental Treatments?

Maine is in line to become the 6th state to pass Right to Try legislation. State Representative Richard R. W. Longstaff (D - Waterville) has introduced a bill which will have a public hearing before the Joint Committee for Health and Human Services on April 6th. The proposed bill (LD180) is titled "An Act To Allow Terminally Ill Patients To Choose To Use Experimental Treatments".

I received an email from the HHS Committee Clerk as I was watching Tweets and Facebook posts from a rally in DC by ALS patients, caregivers and advocates in support of the FDA allowing ALS patients the right to choose to try a drug named GM604. GM604 has passed a small Phase 2A trial. The results of the trial appear promising as have many of this drugs predecessors, which failed to show efficacy in later stages of research. 

However, the failure or success rate of any "experimental" drug isn't the issue. In my view the growing "Right To Try" movement - especially for ALS patients and their families - is about getting the government out of the way of protecting an informed individual from himself.

The fact is, there are very few afflictions for which modern science has failed to find multiple, at least marginally effective drugs and therapies for. In the 76 years since Lou Gehrig put ALS into the public consciousness, the FDA has approved one drug for ALS. That drug is known as Rilutek or Riluzole. Research has shown it to extend life expectancy by three months. A long way from a cure.

There are very few, if any forms of cancer for which there isn't some form of treatment. I'm certain there diseases which are statistically as (or more) rare than ALS which have no cure. My point is, the diseases for which there are no effective treatment to even retard the disease process are few and far between. ALS remains a riddle.

There is much concern in the research community over the Right To Choose. I understand and respect the concerns of researchers who claim giving access an unproven drug, especially to patients who don't meet the trial criteria,  will jeopardize the data that is so important to verifying efficacy. As an ALS patient, I respectfully say: Get over it.

I'm dying. I have a brain that still functions moderately well (although my wife may disagree on some days). There are no options the traditional medical community can offer me, except Rilutek and moral support. With all due respect to alternative practitioners and their patients, been there done that. In my experience if the alternative practitioners had anything of value to offer, they would be open to scientific scrutiny, doing studies and demonstrating the efficacy of their treatments as well. People certainly have the Right To Try alternative medicine. I just remain a skeptic.

So, with no options, a healthy brain and an appropriate level of information, why shouldn't I be allowed to try a drug that has shown promise in a legitimate Phase 1 (or beyond) trial? Should I not be free to risk dying sooner than I might if I didn't try? 

Be careful how you answer that last question. It's a trap of logic. If you answer "No, you don't have the right to try.", then we should ban sky diving and rock climbing. Period. Those are inherently risky activities which present the risk of death. Do healthy people have more freedom to assume risk than the terminally ill among us?

The current drug approval process of the FDA is archaic. It hasn't undergone significant scrutiny or change since it started in the 1960's. Add to that an approval pipeline that is clogged with applications for new toenail fungus and erectile dysfunction drugs, because that's where the money is, and you have a process which doesn't so much protect the public as it does rubber stamp the most profitable products for the pharmaceutical industry. (And yes, I understand that the profits from popular, mass market drugs help fund R & D for other drugs. Just makes one wonder who the FDA really works for.)

Upon first read  Maine's proposed legislation isn't perfect. For example, the draft bill's definition of "Terminally Ill" is: "...a disease or condition that, without life sustaining measures, is reasonably expected to result in death within 6 months." This definition most likely would not cover ALS patients.  It is interesting that the 6 month timeframe aligns exactly with the requirement for a patient to qualify for Hospice care. More interesting is that most, if not all Hospice providers won't provide "life sustaining measures" to patients in their care. So...if the law passes as is, patients will be forced to choose between Hospice and Right To Try.

Regulators, researchers and drug companies have valid concerns regarding Right To Try. They should be part of the dialogue. But they should also be painfully aware that this issue won't go away. Healthcare advocates and families facing terminal disease are demanding the Right To Try. The horse has left the barn, as they say.

Regulators, researchers and drug companies are free to oppose the Right To Try. Just as I should be free to try. Let's all work together to arrive at a solution that works for all, shall we?