At the Pyrenean Holistic Medicine Center, we teach how to reverse neurodegenerative diseases holistically, based on a new medical neuroscience paradigm, supported with strong science. In terms of public policy, it is urgent to better adddres this public health challenge, if only because Alzheimer’s Disease is the most common form of dementia, which the World Health Organisation (WHO) says affects nearly 50 million people worldwide, some 7.7 million new cases per year, the highest incidence of which is in the United States. In conventional medicine, old age is the major risk factor, and there is no conventional therapy to stop or reverse Alzheimer’s symptoms, which include memory loss and disorientation, as well as anxiety, paranoia, confusion, aggressive behaviour and aging acceleration. However in holistic medicine, metabolic disorders promoted by lifestyle aberrations is the major risk factor, one which holistic savor-faire has a good control on.
THE LIMITATIONS OF MAINSTREAM ALLOPATHIC NEUROSCIENCE MEDICINE INSOFAR AS NEURODEGENERATIVE AND ALZHEIMER’S DISEASES ARE CONCERNED
Mainstream allopathic neuroscience medicine has distinguished itself as one of the greatest failures in biomedical therapeutics research and development, from correctly addressing depression, psychosis, schizophrenia, multiple sclerosis, ALS, Parkinson’s to Lewy body dementia, frontotemporal lobar degeneration, amyotrophic lateral sclerosis and the big one, Alzheimer’s disease, who incidence is surpassing the diabetes epidemic.
For AD, there is not a single drug, let alone a combination of drugs, that exerts anything beyond a non sustainable symptomatic effect. To make matters worse, in the past decade, hundreds of clinical trials have been conducted for AD, at an aggregate cost of billions of dollars, without success. In the case of AD, mild cognitive impairment and subjective cognitive impairment, comprehensive combination, innovative and holistic therapies have not even been explored with any seriousness, contrarily to most of the other chronic diseases humankind faces. One of the deep causes that explains this failure is the misguided allopathic model of medicine whose promoters see few if any incentive to perform extensive evaluations of a patient’s mind-body-spirit entity, from his or her hormonal status, nutritional state, toxicity level, gastrointestinal permeability, “leaky brain”, intestinal flora, dental hygiene or other laboratory evaluations presently perceived by mainstream healthcare individual as deviations from the standard of care.
Nonetheless, the past few decades of genetic and biochemical research have confirmed that holistic and innovative medicine is key because an extensive network of molecular and metabolic interactions involved in AD pathogenesis have been shown to exist with a preponderance of the evidence, that which suggests that a network-based holistic therapeutics approach, rather than a single target-based approach, may be potentially more effective for the treatment of cognitive decline due to Alzheimer’s disease and other mental impairment illnesses.
A NEW PARADIGM FOR ALZHEIMER’S DISEASE
Contrary to the medical dogma that Alzheimer’s is caused by the accumulation of sticky amyloid plaques in the brain, we believe that the amyloid beta peptide, the source of the plaques, has a normal and even regulatory function in the brain, as part of a larger set of molecules that promote signals that cause nerve connections to lapse, inter alia, one effect of which is some memory loss. But research has shown that this phenomenon is symptomatic, a mere result of deeper metabolic forces at work, from the imbalance of neurotransmitters and plasticity signaling (1) to a deficiency of key nutrients, an excess of heavy metals and other metabolic abnormalities (2) such as insulin resistance, metabolic syndrome, chronic inflammation (3), hypovitaminosis D, hormonal deficiencies-imbalances, associated with oophorectomy (4), fungi infection (5) and hyperhomocysteinemia (6), among others conditions. Studies such as the European Finger study published in Lancet suggest that metabolic factors may play important roles in the neurodegenerative process (7) while newer 2015 studies suggest that fungus could be a significant factor. Recent results from the evaluation of neural exosomes and nanosomes also support the notion that metabolic abnormalities are present in patients with cognitive decline, often years prior to diagnosis of AD (8), one of which remains the presence of pro-inflammatory cytokines, chemokines, acute-phase reactants, and other mediators of inflammation in AD brains (9).
Despite the corroboration of these showings and the fact that we have identified their corresponding mechanisms of action, most clinical evaluations of patients with cognitive decline do not include extensive metabolic or genomic evaluations that correspond with these findings. We therefore need another neuroscience model, something much more holistic and consistent with strong science.
HOLISTIC PROTOCOL: METABOLIC ENHANCEMENT
Our holistic approach is holistic in nature and non-invasive and even fun in actuality, given the Center’s use of non prescribed superfood molecules, essential oils, alpha-theta brain-waves enhancement techniques, gentle non-invasive forms of ultra sound and musicotherapy, tickle therapy, saunas, heliotherapy, aromatherapy, meditation and, among other techniques, red wine (thanks to resveratrol and other compounds). First off, the holistic approach must be personalized given the fact that there are three subtypes of ADs (10) and that each patient is unique in his or her genomic and epigenomic expression. Second, our holistic approach is hinged on the targeting of many metabolic pathways that affect the plasticity network, including, but not limited to the inflammatory pathways and the energy ATP system, similarly to the cancer challenge, see Center’s holistic cancer reversal program. (11) And lastly, the Center’s holistic approach addresses root causes based on heavy metals overload elimination, nutrient deficiency correction, stress management, food and aromatherapy-based anti-inflammation strategies and sleep enhancement techniques (12), oral health hygiene, fungus targeting and gut permeability reparation, among many others techniques that we teach thanks to which the patient’s symptoms or lesions are better controled (13).
The evidence clearly shows that most of mainstream allopathic neuroscience-based medical interventions for AD and many other neurodegenerative illnesses are based on single target-based approaches which tend to be misguided, dangerous and inefficient. The facts also show that biology does not function well when the medical intervention targets only one pathway. Thus, conventional Alzheimer’s Disease treatment should be based on the targeting of multiple pathways, even with pharmaceutical therapeutics, notwithstanding side or toxic effects, some of which can be managed. Recent advances in allopathic oncology are precisely based on a combination of multiple targeted drugs. Conventional neurosciences should therefore better explore this approach. Meanwhile, in holistic medicine, the golden rule is based on the holistic application of a multi-target synergistic and metabolic approach composed mostly of natural molecules, lifestyle change and healing savor-faire.
(1) In Alzheimer’s disease, there is a fundamental, age-associated imbalance between the dynamically opposed physiological processes that mediate plasticity, i.e., between synaptoblastic and synaptoclastic activity. This signaling involves physiological mediators of synaptic development, maintenance, repair, and remodeling, including APP, its derivative peptides, ApoE, and tau, and is modulated by all of the many disparate factors associated with Alzheimer’s disease. Bredesen DE. Prionic Loops, Anti-Prions, and Dependence Receptors in Neurodegeneration. In: Legname GR, Detlev, editors. Prion Research of Stan Prusiner and his Colleagues. Gernamy: Dusseldorf University Press; 2013. pp. 1–24.
2. Chakrabarti Sasanka, Khemka Vineet Kumar, Banerjee Anindita, Chatterjee Gargi, Ganguly Anirban, Biswas Atanu. Metabolic Risk Factors of Sporadic Alzheimer’s Disease: Implications in the Pathology, Pathogenesis and Treatment. Aging and Disease. 2015;6:282–299
3. Heppner FL, Ransoh off RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16:358–372.
4. Rocca WA, Henderson VW. Is there a link between gynecologic surgeries and Alzheimer disease? Neurology. 2014;82:196–197. Oophorectomy is the surgical removal of one or both ovaries. It is also called ovariectomy or ovarian ablation. If one ovary is removed, a woman may continue to menstruate and have children. If both ovaries are removed, menstruation stops and a woman loses the ability to have children, inter alia.
5. Fungal infection is also observed in blood vessels of AD patients, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identified several fungal species. There is no question that there exists compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals. Yet, the allopathic conventional standard of care does not even recommend anti-fungals. Cf’s Nature’s report: “Different Brain Regions are Infected with Fungi in Alzheimer’s Disease”Diana Pisa, Ruth Alonso, Alberto Rábano, Izaskun Rodal & Luis CarrascoScientific Reports 5, Article number: 15015 (2015)
6. Homocysteine, for example, has been shown to exert multiple effects that may contribute to cognitive decline, such as increasing tau phosphorylation via a post-translational modification-mediated reduction in protein phosphatase 2A (PP2A) function. Zhang CE, Tian Q, Wei W, Peng JH, Liu GP, Zhou XW, Wang Q, Wang DW, Wang JZ. Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus. Neurobiol Aging. 2008;29:1654–1665. Excess homocysteine also promotes glutamate receptor dysfunction, neuronal apoptosis induction, endoplasmic reticulum stress, DNA methylation, mitochondrial dysfunction, vascular damage, and oxidative stress. Moustafa AA, Hewedi DH, Eissa AM, Frydecka D, Misiak B. Homocysteine levels in schizophrenia and affective disorders-focus on cognition. Frontiers in behavioral neuroscience. 2014;8:343.
7. Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385:2255–2263.
8. Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, Kapogiannis D. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology. 2015;85:40–47.
9. Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med. 2006;12:1005–1015.
10. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer’s disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer’s disease, typically affects ApoE4-negative individuals.
11. There are two mechanisms by which cells satisfy their energy needs, oxidative phosphorylation and glycolytic metabolism. The latter includes anaerobic or quasi anaerobic fermentating processes that do not require much oxygen and aerobic mechanisms, such as aerobic glycolysis. As first pointed out by Warburg, oxidative phosphorylation is an evolutionarily more recent, and efficient mechanism of energy generation. However, it requires a high degree of intracellular organization in particular, mitochondrial, and endoplasmic reticulum (ER) networks. Warburg O. On the origin of cancer cells. Science. 1956;123:309–314. The glycolytic type of energy production is evolutionarily more primitive and ancient mechanisms. Although less efficient as compared to oxidative phosphorylation, these mechanisms are more flexible, locally autonomous, and do not require a high degree/extent of intracellular organization and coherence, allowing for fast and flexible adaptations (local and global) in rapidly changing, unpredictable, and/or hostile/offensive environments. Stressed and adapting cells often switch to more flexible, glycolytic modes of energy generation because such modes of functioning increase their chances for survival and successful adaptation in stressful and rapidly changing environments. In fact, proliferating cells seem to switch to glycolytic modes of metabolism during each cell division because they need to dismantle, to renew/duplicate, and to reassemble their cytoskeleton, mitochondrial network, ER, and other organelles each time they divide. Cf. Krisher RL, Prather RS. A role for the Warburg effect in preimplantation embryo development: metabolic modification to support rapid cell proliferation. Mol Reprod Dev. 2012;79:311–320
12. The importance of which is crucial since we now know that sleep is one of the most important brain cleansing mechanism. For aromatherapy and the use of different essential oils like frankincense, see: Rainer E. Use of Frankincense (olibanum) in the treatment of Alzhimer disease. chem ABS. 1996;135:1327–94.
13. AD is characterizedby a build-up of two different types of lesions in the brain. One type, amyloid plaques are a sticky protein that develops between the neurons of the brain and keep them from transmitting properly. The other type of lesion, neurofibrillary tangles, is another thick protein mass or lesion that develops between neurons.
Immune attack: the role of inflammation in Alzheimer disease.
Heppner FL1, Ransohoff RM2, Becher B3.
The past two decades of research into the pathogenesis of Alzheimer disease (AD) have been driven largely by the amyloid hypothesis; the neuroinflammation that is associated with AD has been assumed to be merely a response to pathophysiological events. However, new data from preclinical and clinical studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis. These insights have suggested both novel and well-defined potential therapeutic targets for AD, including microglia and several cytokines. In addition, as inflammation in AD primarily concerns the innate immune system – unlike in ‘typical’ neuroinflammatory diseases such as multiple sclerosis and encephalitides – the concept of neuroinflammation in AD may need refinement.
Nat Med. 2006 Sep;12(9):1005-15.
Inflammation in Alzheimer disease: driving force, bystander or beneficial response?
Alzheimer disease is a progressive dementia with unknown etiology that affects a growing number of the aging population. Increased expression of inflammatory mediators in postmortem brains of people with Alzheimer disease has been reported, and epidemiological studies link the use of anti-inflammatory drugs with reduced risk for the disorder. On the initial basis of this kind of evidence, inflammation has been proposed as a possible cause or driving force of Alzheimer disease. If true, this could have important implications for the development of new treatments. Alternatively, inflammation could simply be a byproduct of the disease process and may not substantially alter its course. Or components of the inflammatory response might even be beneficial and slow the disease. To address these possibilities, we need to determine whether inflammation in Alzheimer disease is an early event, whether it is genetically linked with the disease and whether manipulation of inflammatory pathways changes the course of the pathology. Although there is still little evidence that inflammation triggers or promotes Alzheimer disease, increasing evidence from mouse models suggests that certain inflammatory mediators are potent drivers of the disease. Related factors, on the other hand, elicit beneficial responses and can reduce disease.
Curr Neuropharmacol. 2013 Jul;11(4):414-29. doi: 10.2174/1570159X11311040005.
Natural products as promising drug candidates for the treatment of Alzheimer’s disease: molecular mechanism aspect.
Ansari N1, Khodagholi F1.
Alzheimer’s disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.