Natural therapies for Alzheimer’s
[Disclaimer: I’m not a doctor, only a fan of psychopharmacology. This is just a short review of literature, and none of it should be taken as medical advice.]
A lot of us have aging parents, friends, or are aging ourselves. By 2050, 135 million people will suffer from Alzheimer’s. There are other neurodegenerative diseases out there, too.
There are no known (FDA approved) treatments that halt or reverse Alzheimer’s, but that doesn’t mean there aren’t therapies that work. Natural therapies can’t be patented so they’re under researched, because pharmaceutical companies can’t sell you turmeric, for example.
How Alzheimer’s works
Alzheimer’s is characterized by the development of microscopic lesions in the brain called neurofibrillary tangles. Additionally, proteins fold and gather in a pathological way, forming plaques, or “amyloid-β oligomers”, inside and outside brain cells. Inside brain cells, these are toxic and cause synaptic failure. Meanwhile, extracellular amyloid plaques prevent long-term potentiation (learning) and spread the disease to other neurons. Widespread synaptic loss leads to cognitive decline.
The buildup of toxins, especially heavy metals such as lead and mercury, is thought to contribute to the development of amyloid plaques and Alzheimer’s. Excitotoxicity induced by overactivation of NMDA receptors due to stress may also play a role. In people with genetic predispositions, it’s usually due to mutations in genes that affect the processing of amyloid precursor protein (APP), causing the development of amyloid plaques.
Neuropathology of AD; amyloid oligomers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869993/
Neurofibrillary tangles are microscopic lesions that are the hallmark of Alzheimer’s disease. Synaptic loss
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918894/
How Alzheimer’s spreads through extracellular amyloid plaques
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329309/
Stress contributes to Alzheimer’s; exercise prevents it
It’s important to note that Alzheimer’s (and probably most other neurodegenerative diseases) are stress-related.
In addition to causing cell death through glutamate excitotoxicity, chronic stress is a major cause of oxidative stress and inflammation. These lead to the proliferation of inflammatory cytokines, which kill brain cells and can lead to Alzheimer’s disease. People who are vulnerable to stress or have high levels of anxiety are more likely to develop Alzheimer’s.
This is why meditation and exercise are two recommended activities to prevent disease onset or halt it’s progression. Aside from relieving stress, exercise upregulates BDNF and stimulates adult neurogenesis.
Some natural treatments
I’ll review a few of the plants and treatments I’m familiar with: magnesium, ashwagandha, turmeric, brain-derived neurotrophic factor (BDNF), and psychedelics. More herbs that I haven’t had the chance to review, such as Rhodiola, are also thought to be effective.
So this isn’t a complete list. Lots of other vitamins and herbs are thought to help through their antioxidant or anti-inflammatory properties. For example, this article reviews several Ayurvedic treatments, covering therapeutic plants as well as meditation.
To find the latest research into treatments for Alzheimer’s, you can search PubMed. I like to check “Free abstract” and “Free article” and limit my search to the last few years. Any interesting articles you find will link back to previous research in their introduction. You can also find a review of pharmacological treatments for Alzheimer’s here.
Ashwagandha
Ashwagandha is an herb used extensively in Ayurvedic medicine. Ashwagandha appears to neutralize the neurotoxic effects of amyloid plaques, and prevent the neural atrophy caused by these plaques. In severely stressed mice, it protects against neuronal death in the hippocampus. One of ashwagandha’s compounds, Withanolide A, regenerated the axons, dendrites, and synapses of badly damaged neurons after 13 days of treatment, and restored memory function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576076/
A group of Indian researchers basically showed that ashwagandha is capable of curing Alzheimer’s several years ago. In their study, an extract of ashwagandha reversed cognitive deficits in mice with Alzheimer’s, and removed the majority of amyloid plaques from the brains of middle-aged mice within 30 days. It did this by upregulating (increasing) a protein in the liver.
So you may ask, “Wow, why don’t more people know about this?” It may be because natural cures aren’t profitable. Or because the dose they gave the rats was around 1g/kg. So if you weigh 50kg you’d have to take around 50 grams of this extract a day, which isn’t really feasible and may have side effects. Of course, a lesser dose is probably also effective, though it may not cure Alzheimer’s within 30 days.
How much ashwagandha should you take?
There’s no known lethal dosage of ashwagandha, and it is considered to be very safe though there have been rare reports of drug interactions at high doses. Most ashwagandha supplements contain 300-500mg per pill. Although some brands offer higher amounts of up to 1500mg, there’s no good way of knowing how pure they are and cheaper brands may be less potent. In clinical studies, humans have been given up to 5 grams/day of ashwagandha with no significant side effects. I would suggest 1-2 grams/day long term if you have a neurodegenerative disease.
Neutralizes amyloid-induced toxicity
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077624
By increasing a liver protein, transports amyloid plaques from brain to bloodstream
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295277/
Ashwagandha & Co-Q10 reduce neurodegeneration in Parkinson’s
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067369/
Ashwagandha & Huntington’s disease
https://pubmed.ncbi.nlm.nih.gov/19627208/
Magnesium
A lot of research supports magnesium as a treatment for Alzheimer’s, through various mechanisms. Multiple studies have shown that people with Alzheimer’s tend to be magnesium deficient. (Depressed people also have low magnesium levels, and magnesium has strong antidepressant effects.)
Several studies have found magnesium to improve cognition and memory in patients with dementia. Along with environmental stimulation, magnesium improved cognitive function and memory in mice with Alzheimer’s as well as normal rats.
In another study, seven days of magnesium sulfate injections protected cognitive function and synaptic plasticity, and reversed some aspects of neurodegeneration in a rat model of Alzheimer’s. The magnesium worked by reversing the loss of dendrites, increasing synaptic proteins in the hippocampus, and inhibiting tau hyperphosphorylation, the prelude to the development of neurofibrillary tangles. The results were effective at the level of 100mg/kg but not 50mg/kg. The human equivalent to 100mg/kg would be around 5g (50kg) to 10g (100kg) a day.
Magnesium reduces inflammation and oxidative stress, both of which are associated with the development of neurodegenerative diseases. When administered beforehand it can even prevent neuronal loss from traumatic brain injury.
How does magnesium work?
Magnesium improves synaptic function and learning and memory (facilitating both short-term and long-term potentiation). Similar to memantine (Namenda), an FDA-approved treatment for Alzheimer’s, magnesium regulates glutamate as an NMDA receptor antagonist. As such, it prevents neural atrophy that can result from chronic stress through the overactivation of NMDA receptors. It appears to regulate amyloid precursor protein (APP), the precursor to amyloid plaques. It helps neurons and neural networks grow through activation of the mTOR protein in cells.
How much magnesium should you take?
High doses of 1-5g/day may be most effective in preventing further deterioration or to have a restorative effect on those who have Alzheimer’s, are at risk of dementia, and those suffering from high levels of stress, depression or anxiety disorders.
However doses of 100-400mg per day, taken long-term, are probably enough to exert neuroprotective effects for most people.
Magnesium can be a laxative, and this would be the major side effect at high doses (though some forms of magnesium are better tolerated than others).
Can you take too much magnesium?
Yes, although it’s very hard to take a toxic dose of magnesium. There are rare cases of hypermagnesemia in the elderly. In the reported cases, elderly patients were consuming around 20g/day of magnesium after taking excessive amounts of antacids or laxatives. Kidney problems are a risk factor in developing hypermagnesemia in the elderly.
Curcumin (turmeric)
Curcumin (turmeric) has anti-inflammatory, antioxidant, neuroprotective, chemoprotective properties. Curcumin may be able to halt cognitive decline in Azheimer’s, or prevent the disease’s onset. In animal models, it was able to reverse memory impairment associated with Alzheimer’s.
Pre-clinical and clinical trials involving curcumin for Alzheimer’s are summarized in this very thorough review.
Pre-clinical trials (mice)
AD-like memory-impairment was induced in mice, and then curcumin was administered at 25 and 50 mg/kg for 7 days. Administration of 25 and 50 mg/kg of curcumin reversed memory impairments.
In another mouse model of AD, researchers tested the effect of curcumin (300 mg/kg) and found that curcumin reversed spatial learning and memory impairments while promoting the regeneration of the hippocampus.
Preventative treatment with curcumin protected mice against the neurotoxic effects of amyloid plaques, and prevented apoptosis in the hippocampus.
In older rats, curcumin improved dendritic spine density and dendritic length in the hippocampus and the prefrontal cortex, strengthening neurons and neuroplasticity.
Clinical (human) trials of curcumin
Clinical trials haven’t demonstrated much success. Even a large Chinese study administering 1-4g/day for six months didn’t see an impact on cognitive performance. However this dose was a little short of what preclinical trials were giving the rats, of 25-300mg/kg. There also may have been problems in the curcumin’s bioavailability, which is enhanced by black pepper.
Some special formulations may be better at increasing bioavailability, and appear to be using not only black pepper, but nanocapsules and other technology that can shrink a dose the equivalent of several grams into under 100mg.
Small et al. (2018) evaluated the effect of Theracurmin®, a compound that contains 90 mg of curcumin. Forty non-demented adults between 51 and 84 years of age were randomized to either Theracurmin® or placebo twice a day for 18 months. Visual and verbal, short-term memory as well as attention improved in the Theracurmin® group in comparison to the placebo group. Additionally, brain scans revealed a reduction in amyloid plaque accumulation in certain brain regions of the curcumin group.
Curry & cognitive function in the elderly
https://pubmed.ncbi.nlm.nih.gov/16870699/
Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo*
https://www.sciencedirect.com/science/article/pii/S0021925819630966
Free and nanoencapsulated curcumin suppress β-amyloid-induced cognitive impairments in rats: Involvement of BDNF and Akt/GSK-3β signaling pathway
https://www.sciencedirect.com/science/article/abs/pii/S1074742713001421
Effects of curcumin on memory
https://www.sciencedirect.com/science/article/pii/S1064748117305110?via%3Dihub
The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies
https://www.sciencedirect.com/science/article/pii/S000689931930530X?via%3Dihub#b0340
BDNF
BDNF, or brain-derived neurotrophic factor, is a protein in your brain that’s necessary for the growth of new (and old) brain cells, and key to increasing synaptic strength and plasticity. BDNF not only protects against Alzheimer’s but is a strong antidepressant.
A healthy adult brain produces thousands of new neurons per day in the hippocampus, in what’s called neurogenesis. For these new neurons to develop, they need BDNF, which facilitates the growth of dendritic spines and synapses. Exercise stimulates both neurogenesis and BDNF in the brain. Neurogenesis in the presence of BDNF improved cognitive activity in mice with Alzheimer’s.
What upregulates BDNF? Niacin (vitamin B3), exercise, sunlight, Fingolimod, ketamine, intermittent fasting, sleep, theobromine (chocolate), turmeric, and an “enriched environment”. On the other hand, sugar and stress are thought to limit the brain’s production of BDNF.
The Protective Role of BDNF on Neurodegeneration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589016/#sec4-ijms-21-07777title
Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715325/
Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589016/
BDNF deficiency increases inflammatory cytokines in Alzheimer’s
https://pubmed.ncbi.nlm.nih.gov/31315045/
Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model
https://pubmed.ncbi.nlm.nih.gov/30190379/
Spirituality, meaning, and meditation
Meaning in life negatively correlated with AD
https://pubmed.ncbi.nlm.nih.gov/20194831/
Psychedelics
“The potential for psychedelic compounds to influence and enhance functional neuronal connectivity, stimulate neurogenesis, restore brain plasticity, reduce inflammation and enhance cognition provides a new therapeutic target and compelling argument for further investigation of the potential for psychedelics as a disease-modifying compound in conditions where currently none exists.”
Enhancing neuronal connectivity, stimulating neurogenesis, restoring brain plasticity, reducing inflammation, and enhancing cognition: these are all ways that psychedelics can improve brain health. The main function of psychedelics would be a rapid rebuilding of synapses and neural networks in the brain, which would probably be very good for someone who is at risk of the disease or in early stages.
In one rat neurogenesis was inhibited in the hippocampus at high doses of a psychedelic-like drug. However this effect was acute – they dissected the rat within two hours – they didn’t use LSD or psilocybin, and these are not something one should take every day, so I don’t see this as a major concern.
Higher doses of psilocybin may in mild cases of cognitive dysfunction be more effective at restoring brain connectivity and plasticity. Higher doses in therapeutic settings have also been found to cure depression at high rates, with resolution of symptoms that lasts at least 6 months.
However if patients want to be careful or the disease has advanced significantly, taking a low dose should be fine. A small, barely noticeable dose (such as .5g of psilocybin mushrooms or truffles, every few days) would probably have an effect on restoring synapses.
I don’t know anything about gamma oscillations or interneurons, but apparently they lose power in neurodegenerative disorders, and psilocybin seems to increase their frequency, reducing amyloids, which is a good thing!
In recent studies, enhancing gamma frequency oscillations via external stimuli reduced amyloid burden, possibly via increased microglia activity, and improved cognitive function in rodents (Laccarino et al., 2016; Martorell et al., 2019).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472664/
[Notes on magnesium]
Recent evidence suggests that Mg was implicated in the pathogenesis of AD. Mg levels were decreased in the serum and brain tissues of AD patients in clinical, experimental and autopsy studies (Durlach, 1990; Glick, 1990a; Lemke, 1995; Andrási et al., 2000; 2005; Vural et al., 2010). Moreover, serum Mg levels in AD patients negatively correlated with the Global Deterioration Scale (GDS) and the Clinical Dementia Rating (CDR) (Cilliler et al., 2007). A causal relationship between low Mg in hippocampal neurons and impairment of learning was also demonstrated in aged rats (Landfield et al., 1984). Magnesium deficiency can lead to specific impairments in emotional memory (Bardgett et al., 2005; Bardgett et al., 2007), while magnesium therapy facilitates cognitive function recovery following brain injury; however, there are task and dose- dependent aspects to this recovery (Enomoto et al., 2005; Hoane, 2005; Hoane, 2007). Increasing brain magnesium leads to the enhancement of both short-term synaptic facilitation and long- term potentiation and improves learning and memory functions in rats (Slutsky et al., 2010). Interestingly, treatment of dementia patients with nutritional Mg support efficiently improved memory and other symptoms (Glick et al., 1990b). However, therapeutic administration of Mg is still controversial regarding the treatment of AD, and high doses of Mg may have potential detrimental side effects (Clark and Brown, 1992; Fung et al., 1995; Hallak, 1998; Ladner and Lee, 1999).
https://www.ncbi.nlm.nih.gov/books/NBK507256/#ch18.Magnesium_in_AD
Alzheimer’s disease (AD) is a degenerative neurological disorder that is characterized by synaptic loss and cognitive impairments that include deterioration in learning and memory [1]. AD presents with accumulations of beta-amyloid and tau tangles, along with inflammation and atrophy [151]. Excitotoxicity, neuroinflammation, and mitochondrial dysfunction have all been implicated in Alzheimer’s disease [152], thus, hypomagnesaemia could further impair neuronal function. Factors related to lower magnesium availability, such as malnutrition and poor nutrient intake, are also present in AD patients [153,154], making magnesium deficiency more likely. Additionally, postmortem brain examinations of AD brains have found decreased magnesium levels compared to healthy controls [154,156,157]. Magnesium depletion has been found in the hippocampus in patients with AD, providing more evidence that magnesium may be a target of treatment [156].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024559/
… [39]. These studies revealed that stored and released Mg2+ in mitochondria attenuates the neurodegeneration.
As the NMDA receptor is involved in excitatory neurotransmission, neuroplasticity, and neuroexcitotoxicity, [magnesium] plays an important role in developmental plasticity [146,147], learning and memory [32], and circadian clock rhythm [148].
Mg2+ plays a key role in DNA replication and repair [150].
In developing neurons, the neurotransmitter-induced increase in [Mg2+]cyto mobilized from mitochondria stimulates mTOR activities in a [Mg2+]-dependent manner and facilitates the maturation of neural networks [38]. Typically, mTOR plays a central role in the regulation of the cellular metabolic state and protein synthesis in response to the high demand for growth and proliferation. In neurogenesis, the mTOR activation leads to dendritic arborization via the regulation of protein synthesis [153].
The administration of Mg2+ inhibits the MPP+ neurotoxicity to dopaminergic neurons [203]. (Parkinson’s disease)
Compared with healthy people, AD patients exhibit lower [Mg2+] in the [cerebral spinal fluid] [198,220] and brain [220,221,222]. AD patients with lower [Mg2+] in the serum are likely to show more severe symptoms [223]. Mg2+ deficiency causes emotional memory dysfunction [224,225]. Mg2+ administration improves learning and memory in dementia patients [222] and in healthy animals [30,31,226] and promotes the recovery of cognitive function after brain injury [227,228].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678825/
Magnesium (& Zinc) as an NMDA antagonist?