The Top Researched Natural Treatment Options For Alzheimer’s Disease

by | May 10, 2017 | Herbs, Nutrition, Supplements | 0 comments

The disease known as Alzheimer’s Disease is characterized by dementia which typically begins with poorly recognized memory which slowly becomes more incapacitating. The most common characteristics associated with AD include confusion, poor judgement, language disturbance, agitation, withdrawal, as well as hallucinations. The typical clinical duration of the disease is eight to ten years, but it can range from one to 25 years.

The clinical diagnosis of AD, based on signs of slowly progressive dementia and findings of gross cerebral cortical atrophy on neuroimaging, is correct approximately 80%-90% of the time. Three forms of early-onset familial AD (EOFAD) – caused by mutation of one of three genes (APP, PSEN1, PSEN2) – are recognized.

It is important to note that no cure for Alzheimer’s currently exists, and the drugs currently available to treat the disease have limited effectiveness. It is believed that therapeutic intervention that could postpone the onset or progression of Alzheimer’s disease would dramatically reduce the number of cases in the next 50 years. Ayurvedic medicinal plants have been the single most productive source of leads for the development of drugs, and over a hundred new products are already in clinical development. Indeed, several scientific studies have described the use of various Ayurvedic medicinal plants and their constituents for treatment of Alzheimer’s disease.

There have been several scientific studies, that have described the use of various Ayurvedic medicinal plants termed ‘nervines’ and their constituents to strengthen the functional activity of the nervous system and restoration of memory [8,9]. Phytochemical studies have shown the presence of many valuable compounds, such as lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, that show a wide spectrum of pharmacological activities, including anti-inflammatory, anti-amyloidogenic, anti-cholinesterase, hypolipidemic, and antioxidant effects [5–8,10].

In my post I have shared some common Ayurvedic medicinal plants that have shown promise in reversing the AD pathology.

Here are some herbal treatments that have been used and promoted as memory enhancers in order to help delay or prevent Alzheimer’s Disease.

Here are some of the herbs:

  • Ashwagandha – This herb has been used extensively in Ayurveda as a nervine tonic, aphrodisiac, and ‘adaptogen’ and helps the body adapt to stress [9,11]. Ashwagandha is a member of the nightshade (Solanaceae) family, and the root is the part that is widely used. It is categorized as a rasayana (rejuvenative) and is believed to possess antioxidant activity, free radical scavenging activity, and an ability to support a healthy immune system [12]. Unlike other adaptogens, which tend to be stimulating, Ashwagandha has a calming effect and thus may be particularly indicated in people with AD [13]. A total alkaloid extract of Ashwagandha root exhibited a calming effect on the central nervous system (CNS) in several mammalian species, suggesting the use of this herb to produce relaxation. A recent double-blind, randomized, placebo-controlled study of the effects of Ashwagandha on stress found that it reduced symptoms of stress and inability to concentrate and reversed forgetfulness in a dose-dependent manner, and 500 mg/day was more effective [14]. No additional adverse effects were found.
  • Bacopa Monnieri – Traditionally, BM was used to improve memory and cognitive function [42]. The BM extracts have been investigated extensively for their neuropharmacological effects and their nootropic actions [39,42–44]. In the hippocampus, BM enhances protein kinase activity that may contribute to its nootropic action [45]. BM also inhibited cholinergic degeneration and displayed a cognition-enhancing effect in a rat model of AD [46]. A team of researchers also reported that a standardized extract of BM reversed the cognitive deficits induced by intracerebroventricularly administered colchicines and ibotenic acid into the nucleus basalis magnocellularis [47]. In the same study, BM also reversed the (a) depletion of acetylcholine, (b) reduction in choline acetyltransferase activity, and (c) decrease in muscarinic cholinergic receptor binding in the frontal cortex and hippocampus [47]. BM extracts protected neurons from beta-amyloid-induced cell death by suppressing cellular acetylcholinesterase activity. In addition, BM extract-treated neurons expressed a lower level of reactive oxygen species, suggesting that Brahmi restrained intracellular oxidative stress [48].
  • Cannabis Sativa (Medical Cannabis) – The controversial flower based herb with the psychoactive phytochemical THC or Δ9-Tetrahydrocannabinol has shown strong therapeutic potential for slowing or halting the development of Alzheimer’s. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin’s enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.
  • Caprylic Acid (MCT fat derived from Coconut and Palm Oil) – Caprylic acid is a medium-chain triglyceride (fat) produced by processing coconut oil or palm kernel oil. A food based medicine was created and marketed as “Axona” which had the active ingredient Caprylic acid. The body breaks down caprylic acid into substances called “ketone bodies.” The theory behind Axona is that the ketone bodies derived from caprylic acid may provide an alternative energy source for brain cells that have lost their ability to use glucose (sugar) as a result of Alzheimer’s. Glucose is the brain’s chief energy source. Imaging studies show reduced glucose use in brain regions affected by Alzheimer’s. Axona’s development was preceded by development of the chemically similar Ketasyn (AC-1202). Ketasyn was tested in a Phase II clinical study enrolling 152 volunteers with mild to moderate Alzheimer’s. Most participants were also taking FDA-approved Alzheimer’s drugs. The manufacturer of Axona reports that study participants who took Ketasyn performed better on tests of memory and overall function than those who received a placebo (a look-alike, inactive treatment).
  • Ginkgo Biloba – a plant extract containing several compounds that may have positive effects on cells within the brain and the body.Ginkgo biloba is thought to have both antioxidant and anti-inflammatory properties, to protect cell membranes and to regulate neurotransmitter function. Ginkgo has been used for centuries in traditional Chinese medicine and currently is being used in Europe to alleviate cognitive symptoms associated with a number of neurological conditions. However, results of a large, multicenter Phase 3 clinical trial conducted by several branches of the National Institutes of Health showed that ginkgo was no better than a placebo in preventing or delaying Alzheimer’s disease.
  • Gotu Kola – This ayurvedic herb may have some of the highest potential to improve Alzheimer’s Disease associated symptoms. It has been known to improve memory function in mouse models with Alzheimer’s Disease. Gotu kola, also used in Chinese medicine as a nerve tonic and memory-enhancing agent, appeared to normalize the behavior of mice bred to express a protein mutation that causes Alzheimer’s-like symptoms, according to the study by OHSU and Portland Veterans Affairs Medical Center neurologists. “The gotu kola-treated Alzheimer mice were very similar to wild-type mice, with no significant deficits” on behavioral tests, said the study’s lead author, Joseph Quinn, D., associate professor of neurology, and cell and developmental biology, OHSU School of Medicine and the Portland VA Medical Center He also is an investigator at OHSU’s Layton Aging and Alzheimer’s Disease Center. It is possible some Alzheimer’s patient already are using gotu kola, particularly those who typically experiment with botanical dietary supplements, Soumyanath said. However, “it is not as well-known as ginkgo biloba and it is unlikely that many patients are being directed to this herb by their health care professionals.”But that could change in the coming years, particularly if scientists continue to show gotu kola’s beneficial effects in the lab. OHSU scientists are seeking financial support for additional “preclinical” studies to gather the evidence necessary to justify and design a rational clinical trial in human subjects.
  • Huperzine A – A moss extract that has been used in traditional Chinese medicine for centuries. It has properties similar to those of cholinesterase inhibitors, one class of FDA-approved Alzheimer’s medications. As a result, it is promoted as a treatment for Alzheimer’s disease.The Alzheimer’s Disease Cooperative Study (ADCS) conducted the first large-scale U.S. clinical trial of huperzine A as a treatment for mild to moderate Alzheimer’s disease. Participants taking huperzine A experienced no greater benefit than those taking a placebo.
  • Turmeric – This versatile spice helps detoxify the liver, balance cholesterol levels, fight allergies, stimulate digestion, and boost immunity [28]. Epidemiologic studies show a 4.4-fold lower incidence of AD in Southeast Asian countries where turmeric is commonly used as a dietary spice [29]. Other studies indicate that the non-steroidal anti-inflammatory property of turmeric is associated with a reduced risk of AD [30]. Indeed, when fed to aged mice with advanced plaque deposits similar to those of AD, curcumin reduced the amount of plaque deposition [27,31–33]. It reduced oxidative damage and reversed the amyloid pathology in an AD transgenic mouse [32,33]. Direct injection of curcumin into the brains of the mice with AD not only hampered further development of plaque but also reduced the plaque levels [33]. AD symptoms characterized by inflammation and oxidation were also eased by curcumin’s powerful antioxidant and anti-inflammatory properties [33]. In addition, a low dose of turmeric (160 parts per million, or ppm) reduced proinflammatory cytokine levels that are linked to the neuroinflammatory cascades involved in neuritic plaque pathogenesis [32]. Curcumin’sin vitro ability to inhibit lipid peroxidation and neutralize reactive oxygen species may be several times more potent than that of vitamin E [34].

Here are some other supplement alternatives:

  • Coral Calcium – “Coral” calcium supplements have been heavily marketed as a cure for Alzheimer’s disease, cancer and other serious illnesses. Coral calcium is a form of calcium carbonate claimed to be derived from the shells of formerly living organisms that once made up coral reefs. Coral calcium differs from ordinary calcium supplements only in that it contains traces of some additional minerals incorporated into the shells by the metabolic processes of the animals that formed them. It offers no extraordinary health benefits. Most experts recommend that individuals who need to take a calcium supplement for bone health take a purified preparation marketed by a reputable manufacturer.
  • Creatine Monohydrate – Creatine Kinase works well in the central nervous system. ATP generation, as well as the transfer of high-energy phosphates between these sites by the creatine kinase (CK)/phosphocreatine. The majority of Creatine seems to get taken up continuously through the blood-brain barrier by CRT [48], which works against a huge Cr gradient [54]. Nevertheless, certain brain cells seem to have the capacity for endogenous Cr biosynthesis, especially in the developing brain [51]. Patients with genetic CRT-deficiency lack any detectable Cr in the brain [55] and have severe neurological phenotypes including hypotonia, developmental speech delay, autism, and brain atrophy [55, 56]. These cases emphasize the importance of the substrates of CK, Cr, and PCr, for normal brain function in man.In two studies, Cr supplementation has been shown to improve mental concentration [124], as well as memory and learning [125] in healthy human subjects. It is possible that this will also be true for early stage AD patients.Given the evidence for metabolic dysfunction in AD, we hypothesize that Cr supplementation at an early time point of the disease might be useful in compensating for the disturbed energy metabolism in subjects with AD by replenishing the energy pools, activating mitochondrial respiration [126, 127] and protecting cells from apoptosis [127, 128]. Although Cr cannot increase energy charge if CK is damaged, for example, by oxidative damage (see below), very early in the course of AD, CK is still functioning to some extent, so it is reasonable to assume that Cr may be of benefit in those early phases.Further, CK isoenzymes are known to be prime targets of oxidative damage by free radicals [85–87] that are a hallmark of many neuromuscular and neurodegenerative diseases. The substrate Cr, together with MgADP or MgATP, upon forming a transition state complex in the active site of CK, has a protective effect against inactivation of CK isoenzymes by free radicals, such as oxygen radicals and peroxynitrite. In the case of MtCK, Cr in the presence of nucleotide, additionally prevents the dissociation of native octameric MtCK into dimers [85]. Thus, an elevation of the intracellular concentration of Cr by Cr supplementation may confer additional protection to CK and concomitantly delay the free-radical induced inactivation of the CK system in brain that is seen in AD [87]. Cr might be expected to improve energetic conditions for all cells, as well as for “at risk neurons,” in animal models of neurodegenerative diseases, providing temporary protection.
  • Omega 3 Fatty Acids – Research has also linked high intake of omega-3s to a possible reduction in risk of dementia or cognitive decline. The chief omega-3 in the brain is DHA, which is found in the fatty membranes that surround nerve cells, especially at the microscopic junctions where cells connect to one another. Theories about why omega-3s might influence dementia risk include their benefit for the heart and blood vessels; anti-inflammatory effects; and support and protection of nerve cell membranes. Two studies reported at the 2009 Alzheimer’s Association International Conference on Alzheimer’s Disease (AAICAD) found mixed results for the possible benefits of DHA: The second study—Memory Improvement with DHA (MIDAS)—enrolled older adults with normal age-related cognitive decline. Those who took 900 milligrams of DHA daily scored slightly better on a computerized memory test than those receiving the placebo. MIDAS was conducted by Martek Biosciences, the manufacturer of the DHA used in both studies.
  • Phosphatidylserine – a kind of lipid, or fat, that is the primary component of the membranes that surround nerve cells. In Alzheimer’s disease and similar disorders, nerve cells degenerate for reasons that are not yet understood. The theory behind treatment with phosphatidylserine is its use may shore up the cell membrane and possibly protect cells from degenerating.
  • PQQ (Pyrroloquinoline quinone) – This cofactor can help transfer electrons and helps the mitochondria produce energy. Known as a neuroprotective compound, it helps to protect cognition in animals and humans. A team of researchers at the University of California decided to analyze PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria.Their work, published in 2010, led to several extraordinary discoveries.They found that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development, and function. Cells undergo spontaneous mitochondrial biogenesis through the effects of three signaling molecules activated by PQQ:PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). PCG-1α is a “master regulator” that mobilizes your cells’ response to various external triggers. It directly stimulates genes that enhance mitochondrial and cellular respiration, growth, and reproduction. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity. PQQ triggers a signaling protein known as CREB (cAMP-response element-binding protein). CREB plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, molecular compounds shown to protect and repair cellular DNA. CREB also stimulates the growth of new mitochondria.PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is intrinsically involved in cell function and survival. It has been shown to prevent cell death by combating intensive antioxidant stress, and is of particular importance to brain health and function. DJ-1 damage and mutation have been conclusively linked to the onset of Parkinson’s disease and other neurological disorders.These findings shed light on the results of prior studies where a PQQ deficiency in juvenile mice, for example, resulted in elevated plasma glucose concentrations, a 20-30% reduction in the number of mitochondria in the liver, and consequent impairment in oxygen metabolism. These are hallmark indicators of mitochondrial dysfunction. Additional animal models also suggested significant alterations in mitochondrial numbers. Taken together, these results confirm PQQ’s power to significantly boost mitochondrial number and function the key to cellular anti-aging and longevity.
  • Taurine (Amino acid) – There was a special form known as Tramiprosate, which was tested in a large Phase 3 clinical study as a possible Alzheimer’s treatment.It is a patented variant of the amino acid taurine, which is reported to inhibit the interaction of Aβ with endogenous glycosaminoglycans and thereby prevent β-sheet formation. This drug originated in a screen for low-molecular-weight molecules that mimic glycosaminoglycans and can therefore antagonize the interaction of Aβ with endogenous glycosaminoglycans. Glycosaminoglycans have been shown to promote Aβ aggregation and plaque stability (Gupta-Bansal et al., 1995) has been proposed to interfere with amyloid fibril formation and deposition into plaques.

The biggest challenge to drug and herbal treatments for a disease like Alzheimer’s is the delivery system into the CNS. The delivery of drugs and treatments must be done through bypassing the blood-brain barrier (BBB) as it limits access to the CNS. For decades, the BBB has prevented the use of many therapeutic agents for treating brain-related diseases and injuries, including AD, stroke, brain tumor, head injury, and other CNS disorders. Ayurveda relies on some novel methods of administering herbs or their preparations (or both) to treat CNS disorders. However, proper studies are lacking to demonstrate whether these herbs or their components given orally or by some other means cross the BBB and reach the CNS.

Overall it appears like more research needs to be funded in the study of botanicals and nutraceuticals, in order to find out the effectiveness of long-term usage of herbs as a possible treatment or preventive measure for Alzheimer’s Disease. The future promise of an effective treatment for Alzheimer’s Disease appears to be most closely associated with Ayurvedic based herbal supplementation.

References:

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