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Alzheimer's disease

Microdose lithium formulation is capable of halting signs of advanced Alzheimer’s and improving cognition

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microdose lithium formulation and alzheimer

In a new study, a team of researchers has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology and of recovering lost cognitive abilities.

The above snippet is from a press release published last month on Science Daily: Can lithium halt progression of Alzheimer’s disease? Keep in mind that this is an animal study but the results are so promising.  I’m also very intrigued by the delivery method (more on that below).

In order to give this microdosing context, a typical adult prescription for is 900-1800mg lithium carbonate/day.  I reached out to the lead author for clarification about the dosing of this new formulation and lead researcher Dr. Cuello shared this with me:

I calculate that our lithium dosage is 285 times lower concentration than the 900 mg dose (based on 70 kg of body weight) and 570 times lower than the 1800 mg dose.

This translates to around 3.2 mg to 6.4 mg NP03 based on 70kg of body weight (which is around 154.3 lbs).

NP03 is a disease-modifying nano dose formulation of lithium citrate which is used sublingually. I assume it’s not yet commercially available.

Also from the press release: “our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications.”

Here is a link to the actual paper: NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats

Can we compare NP03 to low dose lithium orotate?

What is really interesting is that low dose lithium in the form of lithium orotate is commonly recommended by integrative practitioners for anxiety, mild mood swings, brain fog, ADHD and insomnia. I have found it to be extremely beneficial for many of my clients and have used it personally with success (for brain fog and insomnia).

Just how much lithium orotate is low dose? Typical doses are 5-10 mg per day, increasing to 20mg per day.

Can we compare NP03 to low dose lithium orotate? It’s too early to know for sure but we I believe we can start to make extrapolations, especially given that both are very low doses.

Integrative psychiatrist, Dr. James Greenblatt, MD has written extensively about low dose lithium orotate for the above purposes and for Alzheimer’s too. In this article, Lithium: The Cinderella Story About a Mineral That May Prevent Alzheimer’s Disease, he shares that

Scientists first became interested in the use of lithium for treating neurodegenerative disorders when they observed that bipolar patients using lithium therapy seemed to have lower rates of cognitive decline than peers on other medications.

He writes how an enzyme called Glycogen Synthase Kinase-3 (GSK-3) – a serine/threonine protein kinase – normally plays a major role in neural growth and development and how lithium

works as a direct GSK-3 inhibitor… halting inappropriate amyloid production and the hyper-phosphoryation of tau proteins before they become problematic.

If all this fascinates you as much as it does me, Dr. Greenblatt writes more about lithium orotate in his excellent book: “Nutritional Lithium: A Cinderella Story: The Untold Tale of a Mineral That Transforms Lives and Heals the Brain” (my Amazon link).

Alzheimer’s and cognitive decline have many root causes

Keep in mind that Alzheimer’s and cognitive decline have many root causes that must be considered. This may include inflammation, stress and candida, and even insecticide exposure.

Benzodiazepines have also been linked to increased Alzheimer’s risk which is why a nutritional approach for anxiety is the best approach. Let’s use the amino acids like GABA (for physical anxiety), and tryptophan (for worry and fears), as well as dietary changes and improving gut health instead of anti-anxiety medications.

The best Alzheimer’s book

The best Alzheimer’s book is “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline” by Dr. Dale Bredeson (my Amazon link). He doesn’t mention lithium orotate so I look forward to hearing his thoughts on this new research. [I’ll come and update the blog when I do]

You can read about some of Dr. Bredesen’s work here: Alzheimer’s disease, mercury and mycotoxins

I look forward to human clinical trials of NP03. Dr. Cuello “ believes that there is an excellent opportunity to launch initial clinical trials of this formulation with populations with detectable preclinical Alzheimer’s pathology or with populations genetically predisposed to Alzheimer’s, such as adult individuals with Down Syndrome.”

I would also love to see lithium orotate compared to NP03 in future research.

In the meantime I feel this early research is exciting because it supports some of what is being seen clinically with lithium orotate.

Have you used lithium orotate with success? How much has helped you and have you seen cognitive benefits? What about a more even mood, better sleep and less anxiety?

And have you or a family member seen improvements with the Bredesen protocol?

Alzheimer’s disease: address the root cause to reverse symptoms (Microbiome summit)

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Dr. Jill Carnahan’s interview on the Microbiome Medicine Summit 2 covers cutting edge new information about Alzheimer’s disease, based on the work and research of Dr. Dale Bredesen. They start with the gut-brain connection and Dr. Carnahan shares this:

we used to think of early-onset cognitive decline and dementias and mood disorders as being in their own bucket. And so, we saw psychiatrists or neurological doctors or neurologists to treat those diseases. And now we’re finding as we knew for several years with functional medicine that, obviously, it’s all connected.

And the gut is especially important because this reservoir holds so many of our microbes and possibly pathogens and that speaks to the brain through the vagus nerve and through cytokines and through inflammatory molecules of all types.

And so, this conversation between our gut and our brain is very profound and has a huge impact on things like multiple sclerosis or dementia, Alzheimer’s, or even things like bipolar disorder, schizophrenia, depression, anxiety, and sleep disorders.

So what we’re finding is by addressing the immune system and the gut which are intricately connected, we can often get profound effects on areas in the body that are far from that, like the brain.

Dr. Kellman asks Dr. Carnahan to share a study that will be the slam dunk for really believing in this connection and she mentions a paper titled Microbes and Alzheimer’s Disease. It cites pathogens like herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete which can affect the brain and play a role in Alzheimer’s disease.

Dr. Carnahan then covers Dr. Dale Bredesen’s subtypes of early-onset dementia which allows you to treat the root cause and actually reverse symptoms. She goes into it in great detail so I’m going to give you the summary version here:

Type #1 is inflammatory

  • This could be from inflammation or infections or other poor dietary habits. And that’s where the microbiome could play into that.
  • You might see elevated CRP, IL-6, TNF-alpha. You might see a low albumin to globulin ratio. You might see high homocysteine, hypothyroid, elevated cortisol

Type #1.5 is glycotoxic

  • The pure pre-diabetic, diabetic
  • That’s kind of the pure elevated insulin, elevated fasting blood sugar, elevated cortisol, low testosterone, high triglycerides, low HDL (and has an element of inflammation)

Type #2 is atrophic: So that’s someone who loses their trophic factor of support like estrogen, testosterone, insulin, and vitamin D3.

And often, these type 1s and type 2s actually have ApoE-4 double mutations which are higher risk for Alzheimer’s.

Type #3 is toxic:

  • Toxic mold exposure, biotoxins from Lyme disease, or heavy metals or other chemicals.
  • Often these chemicals will act on the tight junctions of the gut and increase permeability. And then that permeability leads to massive endotoxemia.
  • Younger onset of symptoms (like 40s and 50s) and reversible once you find and remove the root cause

Type #4 is vascular: inflammation of the blood vessels, high homocysteine

Type #5 is traumatic: wrestlers or boxers or football players that have had multiple head injuries or trauma.

By addressing the various root causes, Dr. Bredesen reports a reduction and in some instances reversal of dementia symptoms.

Of course, we know anxiety is common when it comes to Alzheimer’s and dementia. By addressing many of these above root causes we’re also able to reduce anxiety symptoms at the same time.

It was a fascinating interview and I hope you enjoy it as much as I did. I learned a great deal and find it very useful to group the symptoms into types.

There does seem to be one aspect that Dr. Carnahan didn’t address and I haven’t seen it covered in Dr. Bredesen’s papers: the impact of benzodiazepines on dementia and Alzheimer’s disease.  There is conflicting research on this but I feel there is enough research that does show a correlation – enough for us to be concerned.   Here is a recent paper looking at high-dose benzodiazepine use in Chinese patients , supporting an association.

This 2016 paper – Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis states:

Our results suggest that benzodiazepine use is significantly associated with dementia risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

This may likely fall under type #3 (toxic).  I plan to reach out to them as a follow-up.

UPDATE: May 9, 2017.  I did hear back from Dr. Carnahan and she shared that she always discusses history and physical and lab testing, and history of benzodiazepine use or other neuroactive substances. 

And new research shows that it’s more than the benzodiazepines: SSRIs, SRNIs and atypical antipsychotics increase the risk of dementia in veterans with PTSD and even in those who don’t have PTSD. 

I hope you’ll join the host Dr. Raphael Kellman and all the great speakers on the Microbiome Medicine Summit 2, May 8-15, 2017 to learn more.

If you have questions or comments please feel free to share in the comments.