Preventative medicine for neurodegenerative conditions, disease

If global dementia were a country, it would be the 18^th largest economy, said David Perlmutter, MD, FACN, ABIHM, neurologist, author, and lecturer at Empowering Neurologist, at the 2019 Integrative Healthcare Symposium in New York City.  

It’s costing us over $1 trillion to treat dementia, which is expected to rise $2 trillion by 2030. Many blame genetics, but the increase is not a sudden genetic change, Perlmutter said, but the environment.

“The good thing is these are variables we can control,” said Perlmutter, “which is especially good for a disease that has no pharmaceutical treatment.”

And yet, so many individuals hand the responsibility to the physician.

“It’s time to hit the ball back to the other side of the court,” said Perlmutter. “That’s why we’re here.”

The pharmaceutical industry is losing its battle in terms of developing a magic bullet for Alzheimer’s disease. The answer is not the development of a drug, said Perlmutter.

Lifestyle is what matters when it comes to brain health, he said. These are factors over which we have control. Poor diet and other lifestyle choices bring on insulin resistance, loss of memory, and eventually neurodegenerative disease. Preventative medicine should start at the top, well before onset of neurodegenerative disease.

“We don’t have anything at the bottom to mop up inappropriate lifestyle choices,” said Perlmutter. “We’ve got to stop trying to mop up the problem and we’ve got to shut off the faucet.”

A 2016 study published in the journal Frontiers in Molecular Neuroscience looked at the conventional notion that regional brain glucose hypometabolism can be present long before the clinical diagnosis of Alzheimer’s. Simply put, areas with neuronal degeneration use less fuel.

However, even in Alzheimer’s, while there is regional hypometabolism of glucose as fuel, ketone utilization is preserved, said Perlmutter. There are multiple examples of conditions in which risk for Alzheimer’s is elevated and regional brain glucose hypometabolism is present before the clinical onset of the disease. One example is insulin resistance.

Insulin resistance starts with chronic sedentarity and a high carbohydrate diet. From there, it leads to hyperglycemia, hyperinsulinemia, and insulin resistance, which then results in glucose hypometabolism, decreased ketogenesis, and decreased ketone metabolism.

Ketones have been fundamental for human survival. They are more efficient for ATP production compared to lipids and glucose. They reduce oxidative stress and histone deacetylase inhibitory activity. They also encourage G-protein stimulation and upregulation of BDNF production.

Another 2005 study looked at women with mild insulin resistance due to polycystic ovary syndrome (PCOS). The traditional treatment for PCOS is oral contraceptives, metformin, or bariatric surgery. Study participants were placed on a diet with 20 grams or less carbohydrates daily for 24 weeks. Five women completed the study, and saw a decline in body weight, free testosterone, and fastiang insulin.

 Finally, a 2017 study showed that midlife inflammatory markers are associated with smaller late-life brain volume. Lifestyle factors are some of the leading causes of inflammation.

These studies summarize Perlmutter’s idea that age-related disease prevention should start as early as possible.  For this, he recommends following a ketogenic diet.

There are multiple reasons why the ketogenic diet is an ideal preventative approach to Alzheimer’s disease and other age-related diseases. Ketones are a brain super fuel, Perlmutter said, and when the brain cells are powered with ketones, they can produce energy or ATP molecules much more efficiently gram for gram in comparing using ketones for fuel versus carbohydrates, but also do so with less production of damaging free radicals, which are kind of like the exhaust of brain metabolism. So, less exhaust, less damaging free radicals, and higher levels of these ATP molecules.

We know that a ketogenic diet that reduces inflammation in the human body, and as such it is reducing that fundamental mechanism that underlies Alzheimer’s and Parkinson’s, and diabetes, and coronary artery disease and, really, across the board all the chronic degenerative conditions, said Perlmutter. We also know that ketones specifically one ketone, beta-hydroxybutyrate, amplifies the gene transcription to make BDNF. Again, that’s key to increasing the growth of new brain cells, increasing the connection of brain cells which we could call neuroplasticity or synaptogenesis, but also BDNF is important in protecting brain cells against trauma.

A ketogenic diet helps increase insulin sensitivity. Insulin plays a very important role in keeping the brain functional. We need insulin functionality in the brain not only because of how it delivers glucose to the brain. Insulin in the brain also acts as a trophic hormone and improves the functionality of brain cells.

Finally, we know that beta-hydroxybutyrate acts to stimulate guanine nucleotide-binding proteins (g proteins), and these g proteins regulate immune function, regulate inflammation, and regulate the vitality and functionality of brain cells.

“Food is more powerful than drugs,” said Perlmutter. “It all starts with lifestyle choices.”