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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?

Theanine for easing stress and anxiety, and improving cognition and sleep in healthy adults

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theanine for anxiety

L-Theanine is a “unique non-protein amino acid found in green tea” which according to the study below, has shown benefits when used short-term or acutely as a supplement for it’s anti-stress effects, reducing anxiety, improving sleep quality, improving cognition and even easing depression.

This 2019 study, Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial, aimed to examine the effects of four weeks use of l-theanine:

on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; aged 20-69) who had no major psychiatric illness.

The trial was randomized, placebo-controlled, crossover, and double-blind.

L-theanine (200 mg/day of Suntheanine), was used by study participants before going to bed each night and was used for four-weeks.

Study participants who used the theanine for two weeks observed the following:

  • For sleep: Reductions in sleep latency (the amount of time it takes to fall asleep), sleep disturbance and less use of sleep medication
  • For cognitive function: Improvements in verbal fluency (especially letter fluency) and improvements in executive function (planning, multi-tasking etc)

The Japanese versions of The Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased and the study concludes as follows:

Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.

The authors also note that “there were no significant adverse events, demonstrating the safety of four weeks of L-theanine administration.”

As expected, the participants saw increases in serum theanine concentrations. What is unusual and inconsistent with previous studies, is the fact that there was “no significant effect on cortisol or immunoglobulin A levels in the saliva or serum.” I’m not sure I understand  the reasoning they propose i.e. that “the reduction of salivary cortisol and immunoglobulin A levels may be short term, recoverable effect of L-theanine administration.”  I’ll be digging deeper into this to try and get a better understanding of these differences.

Some of the reported possible mechanisms of action

Here are some of the reported possible mechanisms of action of theanine from some studies referenced in his paper:

  • via glutamate receptors (improving cognitive dysfunction)
  • as a neuroprotective agent and “increases in brain serotonin, dopamine, GABA levels” (improving mood and focus and reducing anxiety)
  • enhances hippocampal activity (the hippocampus has a major role in learning and memory)
  • via a proposed increase in the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus (BDNF is a protein implicated in the stress response, long-term memory, Alzheimer’s disease, and psychiatric disorders)

Theanine or GABA – which one to use when?

I typically start my clients with a trial of GABA Calm for low GABA symptoms like physical tension, stress and overwhelm, panic attacks and insomnia. If we are not getting all the expected benefits with GABA and there is a need for added cognitive benefits then we’ll consider adding theanine too. Some folks find one works better than the other and some like a combination (at the same time or theanine in the day/GABA at night or GABA in the day/theanine at night).

I recently reached out on facebook asking: “Theanine or GABA? Which do you prefer for anxiety and why? How much helps? And any other benefits (like reduced body pain, better thinking/cognition, easing IBS gut pain, reduced cravings, less negative self-talk etc)?Or do you like a combination of both?”

As you can see from these varied responses it’s a matter or trialing both to find what works for each person’s unique needs:

  • Lorraine shared this: “They are both good, but I reach for GABA Calm first.. 2 or 3 lozenges. If anxiety doesn’t leave quickly with GABA ( which works well for a panic attack), and I continue to have anxiety humming along in the background, then I’ll reach for theanine.”
  • Jackie shared this: “I take 200mg theanine in morning, then 100mg GABA around 4pm, when the kids get home from school. I had a panic attack in the middle of the night last week, took GABA 100 mg, then seemed to calm down.” I asked if theanine gives her a feeling of calm focus and she said: “yes, I think so. I noticed if I take 200mg of GABA, it makes me drowsy.”
  • Evelyn shared this: “I use both at night for sleep. If I could only use one it would be l-theanine.” Theanine is more consistently helpful for stress reduction and sleep for me. I use 200mg. When I use GABA it’s 500mg of chewables.”
  • Sara shared this: “GABA during the day, theanine at night.”
  • Karine shared this: “GABA!! The Source Naturals Theanine Serene with Holy Basil is really good. But GABA Calm (also Source Naturals which is a sublingual lozenge) is the only thing for a severe issue/episode and helps me concentrate right before an important presentation at work etc. Pure GABA from any supplier is good for long periods where you need a boost or to tone down general anxiety. I also bought a probiotic that also includes GABA (Jarrodophilus Mood) and notice it improves digestion too.”

You can find my favorite GABA/theanine combination product, a theanine-only product and my most popular GABA products on the supplements blog here (and with details for how to set up an account for my online store)

Nutritional Fundamentals for Health GABA-T SAP: 300mg GABA, 150mg theanine. This is pleasant-tasting when opened on to the tongue and works very well when GABA Calm can’t be used.

Pure Encapsulations L-Theanine: 200mg theanine. This is also pleasant-tasting when opened on to the tongue. Unlike like GABA, it can also be swallowed.

Source Naturals GABA Calm. This is a pleasant-tasting sublingual product that is my most popular and most effective form of GABA I use with my clients. It can be used in conjunction with theanine.

Enzymatic Therapy GABA: 250 mg GABA. This is also pleasant-tasting when opened on to the tongue and works very well when GABA Calm can’t be used. It can also be used in conjunction with theanine.

Please let us know … theanine or GABA: which do you prefer for anxiety and why? How much helps? And any other benefits (like reduced body pain, better thinking/cognition, easing IBS gut pain, reduced cravings, less negative self-talk etc)? Or do you like a combination of both?”

Treating Neuroinflammation Course by Dr. Datis Kharrazian

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treating neuroinflammation course

Dr. Datis Kharrazian is a Harvard Medical School-trained researcher and author of Why Isn’t My Brain Working. The Treating Neuroinflammation Course is based on breakthrough research into the role glial cells – the brain’s immune cells – play in neuroinflammation. Dr. Kharrazian has exhaustively studied this new research and developed new clinical models he’s used to treat his patients. Now he’s ready to teach them to you.

In the Treating Neuroinflammation Course you will learn:

  • The role of the brain’s immune cells, called glial cells, in maintaining the health of the neurons.
  • How focusing on the neurons but ignoring glial cells explains why functional neurology protocols often worsen symptoms or fail.
  • How glial cells that have become pro-inflammatory actually change in shape, anatomy, and function… and what to do about it.
  • Clinical strategies for disarming activated glial cells.
  • How to figure out what is causing neuroinflammation in each patient; it will be different for each.
  • How to stimulate the neurons to keep glial cells healthy.
  • How to prevent accelerated degeneration and loss of glial cells and take care of the ones you and your patients have left.
  • How to work backwards through a step-by-step clinical process to uncover each patient’s unique triggers for neuroinflammation.
  • How memory, cognition, synaptic function, neurotransmitter activity, and other vital brain functions are dependent on healthy glial cell function.
  • Research breakthroughs in what causes glial cells to become pro-inflammatory.
  • How to identify patterns of neuroinflammation on blood tests.
  • How healthy glial function supports positive neuron plasticity.
  • How gut bacteria directly communicate with glial cells.
  • How to use physical examinations and neuroimaging studies to identify neuroinflammation and track the progress of protocols.

Here is my video interview with Dr. Kharrazian sharing some highlights from the Treating Neuroinflammation course.

One of many gems he shared: when you hit your head, whether it’s a mild bump or if you’re concussed or lose consciousness or have a very severe traumatic brain injury (TBI), the severity of the neuroinflammation depends on many factors including your blood sugar levels, if you have an autoimmune condition and many other factors outside of the injury itself.

We talk about the fact that registration for this training does include ongoing access to case discussions on the private Facebook group. Two of the case studies will be followed live over the next few months. One gentleman who has volunteered to be a case study, has already introduced himself in the Facebook group. To me, this adds so much value to the course because we almost get to shadow Dr. Kharrazian in real life.

If you’re already signed up for the course, enjoy this video and I’ll see you in the course Facebook group (be sure to tag me and say hi). I am loving the interaction with the other practitioners and the training hasn’t even started.

If you’re not yet signed up and are still considering it, registration for the LIVE and LIVESTREAM does closes Wednesday, May 15th at 11:59 p.m. (PST). It will be available on-demand after this date at some time in the future but I don’t have those details.

dr. Kharrazian

I had the good fortune to attend a number of live trainings with Dr. Kharrazian shortly after becoming a nutritionist and I’ve been a huge fan ever since then. I’ve always been impressed with the depth of his knowledge.

Here are a few endorsements from prominent functional medicine practitioners:

mark hyman

Dr. Kharrazian has been a prominent educator and highly-respected clinician in the functional medicine community since the inception of functional medicine. He is an expert clinician and an innovator in this field ~ Dr. Mark Hyman

dave perlmutter

Dr. Kharrazian’s work represents the vanguard in our understanding of the role of lifestyle choices in charting the brain’s destiny. His highly effective educational outreach has opened the door for countless healthcare providers, allowing them to dramatically increase their effectiveness in treating and indeed preventing so many of the pernicious conditions that plague our modern society ~ Dr. David Perlmutter

This training is geared to practitioners BUT health-savvy patients/clients are welcome to attend too:

The neuroinflammation course is not actually practitioners-only. Dr. Kharrazian welcomes anyone to sign up for the course, and there are already a number of non-practitioners enrolled. Over on the Kharrazian Institute facebook page, he addresses this in some of the threads. There will be content that moves a bit too fast for those who do not have medical training, but for the avid patient who is well-read and keen to learn on a deeper level, the course is open. More info can be found on the Kharrazian Institute FAQ page.

Details and registration for The Treating Neuroinflammation Course here

Tryptophan promotes charitable donating

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This 2014 study is one of my all-time favorite applications of tryptophan, an amino acid I use extensively with anxious clients. The goal of the study, Tryptophan promotes charitable donating, was to investigate the link between serotonin and charitable giving, something the authors consider to be “one of the most important elements of prosocial behavior.” They offer this quote by Molière:

Every good act is charity. A man’s true wealth hereafter is the good that he does in this world to his fellow.

In this study they tested whether charitable donating or giving can be promoted with the use of the amino acid tryptophan, the biochemical precursor of serotonin:

Participants were compared with respect to the amount of money they donated when given the opportunity to make a charitable donation.

Additional information about the study

Here is some additional information about the study, where the study group was given 800mg of tryptophan:

Thirty-two healthy international south European students (mean age = 21.8; 4 male, 28 female; mean Body Mass Index = 21.5, range 17.8–30.8) with no cardiac, hepatic, renal, neurological, or psychiatric disorders, personal or family history of depression, migraine and medication or drug use participated in the experiment.

Sixteen participants (2 male, 14 female) were exposed to an oral dose (powder) of 0.8 grams [which is 800mg] of tryptophan – which roughly corresponds to the amount of TRP contained in 3 eggs–and 16 (2 male, 14 female) to 0.8 grams of microcrystalline cellulose, a neutral placebo. These doses were always dissolved in 200 ml of orange juice.

The donating task was standardized, without the presence of an experimenter, and with a fixed amount of money in a fixed number of notes and coins:

…Participants were not informed beforehand that the donating task was part of the experiment. Donating behavior was measured by the amount of money the participant donated. After having received 10 Euros… for their participation in the study, participants were left alone and asked whether they were willing to donate part of their financial reward to charity. Four money boxes (Unicef, Amnesty International, Greenpeace, and World Wildlife Fund) had been positioned on the table.

Here are the results:

As expected, compared to a neutral placebo, [tryptophan] appears to increase the participants’ willingness to donate money to a charity.

The serotonin oxytocin connection

The authors mention the “functional and anatomical interactions between serotonergic and oxytocinergic systems” and that “it may be likely that the willingness to donate money to a charity is modulated by the effect that serotonin exerts on oxytocin levels.”

My perspectives

I always like to add my perspectives on studies like this so here goes. We know that because tryptophan boosts serotonin it’s going to improve mood and reduce anxiety, worrying and fears. When you feel better, lighter, happier and calmer you feel like anything is possible and I can see how this could translate to feeling more caring and wanting to be charitable.

The authors do mention how low serotonin is correlated with “antisocial behaviors such as social isolation and aggression.” Anger and irritability is also something we see when serotonin is low. Of course, these are also antisocial behaviors.

Here is the amino acid questionnaire with the low serotonin section.  I’d like to add this new sign to the questionnaire and wonder what would work: Lack of charitability? No desire to give to charity?  

One additional comment is that with the work I do, the amino acids are used when you show signs of low serotonin such as anxiety or worry or depression or insomnia or afternoon/evening cravings. I use the trial-response method to determine if you’ll actually respond to tryptophan i.e. experience benefits and how much you will need to see those benefits. I starting dose is typically 500mg tryptophan and I have found the Lidtke brand to be the most effective. You can read more on tryptophan here.

Because of this I’m intrigued with this application of using tryptophan in healthy individuals. But I’d also be cautious based on what I’ve seen with clients who don’t need serotonin support and take tryptophan – they can feel too sleepy or even more sad or more anxious. This would be my hesitation in saying we should give everyone tryptophan in order to create a more charitable and giving society. I do however agree with the authors about the importance of a quality real whole foods diet with adequate quality animal protein, saying the study result:

supports the idea that the food we eat may act as a cognitive enhancer modulating the way we think and perceive the world and others.

The lead author, Professor Laura Steenbergen, works in the Cognitive Psychology Unit, Institute for Psychological Research and Leiden Institute for Brain and Cognition, Leiden University Leiden, Netherlands, as is doing some very interesting research with amino acids, cognitive enhancement and mood improvement. It’s really exciting!

We’d love to hear if you feel more charitable and giving when you take tryptophan or 5-HTP (since it also boosts serotonin)?

And if you feel more charitable and giving when you eat a quality real whole foods diet with adequate quality animal protein?

Berries: cognition, PTSD, inflammation, microbiome, anxiety and depression

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Berries such as blueberries, raspberries, raspberries and strawberries have so many health benefits, including but not limited to improving cognitive function, offering benefits for PTSD (post-traumatic stress disorder), reducing inflammation and even increasing good bacteria in our gut. There are even initial promising results of a compound in blackberries having antibiotic like properties against drug-resistant bacteria MRSA (methicillin resistant staphylococcus aureus).

Blueberries improve cognition

In a 2017 randomized, double-blind, placebo-controlled trial, dietary blueberries were found to improve cognition among older adults

In this study, 13 men and 24 women, between the ages of 60 and 75 years, were recruited into a randomized, double-blind, placebo-controlled trial in which they consumed either freeze-dried blueberry (24 g/day, equivalent to 1 cup of fresh blueberries) or a blueberry placebo for 90 days.

The findings show that the addition of 1 daily cup of blueberries to the diets of older adults can improve some aspects of cognition, such as

…significantly fewer repetition errors … in the California Verbal Learning Test (CLVT), a neuropsychological test which can be used to assess verbal memory abilities.

… fewer errors on trials when they switched to a new task as part of a task-switching test. Task switching is an important component of executive function, a collection of brain processes that are responsible for guiding thought and behavior.

This research was funded by the U.S. Highbush Blueberry Council.

Blueberries boost serotonin and ease PTSD

A study presented in 2016 reports that blueberries boost serotonin and may help with PTSD and anxiety. This was an animal study where the traumatized rats were fed a blueberry-enriched diet. The study authors report an increase in serotonin levels and suggest that these findings

indicate non-pharmacological approaches might modulate neurotransmitters in PTSD.

Presumably this could help if you have anxiety and depression too, since low serotonin is often one of the underlying factors.  

Anti-inflammatory activity of berry fruits

A 2016 study compared the anti-inflammatory and antioxidant effects of extracts of Lycium barbarum (found in goji berries), Vaccinium macrocarpon (found in cranberries) and Vaccinium myrtillus (found in blueberries).

High amounts of phenolic compounds, including rutin, were identified in all berries extracts. Quercetin was identified in blueberries and cranberries. Hepatic/liver concentrations of glutathione were higher in animals treated with goji berry extracts. Overall the study reports that:

These results suggest that quercetin, rutin, or other phenolic compounds found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress.

We know that inflammation plays a role in mood issues so this is yet another mechanism for supporting your body nutritionally.

Wild blueberry powder drink increases bifidobacteria in the human gut

Wild blueberries are a rich source of polyphenols, fiber and other compounds that are metabolized by the intestinal microbiota. A 2011 human study reports that six weeks of consumption of a wild blueberry (Vaccinium angustifolium) drink can positively impact the composition of the intestinal microbiome, by increasing levels of Bifidobacterium.

There are numerous studies showing the benefits of bifidobacteria probiotics on mood and anxiety. Here are a few of them:

Blackberry compound as an antibiotic against MRSA?

This section doesn’t involve eating blackberries but I’m including it because I just love this story, it’s inspiring and it has not received any coverage in the mainstream media. An article in a local publication reports that Irish teen wins top science prize for blackberry antibiotic that fights resistant bacteria

A 15-year-old science student Simon Meehan of Coláiste Choilm won first place in the 54th BT Young Scientist & Technology Exhibition. His discovery is that chemicals found within blackberries could form antibiotics that kills Staphylococcus aureus – often known as MRSA and well known for being resistant to antibiotics.

And he says his grandfather – a herbalist – was the inspiration that kept him going, keeping a frame picture of him at his side whilst he worked.

Professor John O’Halloran, who helped judge the competition, was fulsome in his praise for Simon’s work: “This is a really exciting project which explores the possibility of the blackberry leaf extracts’ ability to control harmful bacteria. The unexpected findings deliver a unique approach to killing bacteria using natural plant active ingredients.

You can watch a video of Simon Meehan sharing more about this investigation and the result here:

Simon Meehan of Coláiste Choilm, Cork investigates the antimicrobial effects of aerial & root parts of selected plants against Staphylococcus aureus.

Here are some ways to enjoy berries in your diet:

  • Fresh berries as a healthy snack
  • Berries like blueberries are quite delicious when eaten frozen too – kids often love them like this
  • In a smoothie for breakfast, together with coconut milk, a banana and some whey, pea or other quality protein powder (great for good blood sugar control/hypoglycemia and reducing anxiety and irritability too)
  • As a dessert with grass-fed organic ice-cream or cream, or coconut milk if dairy is an issue for you
  • Dunked in melted dark organic free-trade chocolate as an occasional treat
  • Freeze-dried or dehydrated berries as a camping or travel snack

Make sure to buy organic berries as non-organic are on the Dirty Dozen list and are highly sprayed with pesticides.

How do you enjoy eating your berries and how often do you eat them?