Editor’s Note: This is an edited version of an article that originally appeared in Focus Newsletter’s Spring 2017 issue.
Neurodegenerative condition (ND) is an umbrella term for a range of conditions which primarily affect the neurons in the human brain, but can also affect the spinal cord1 and peripheral nerves.2 NDs are thought to be incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells.3 A naturopathic approach can often slow down the progression of the neuronal degeneration, as well as strengthen the central and peripheral nervous systems, decrease oxidative stress4 and optimize mitochondrial function.5
Toxic Exposures: The First Place to Look
First and foremost, I investigate the patient’s history of past and current toxic exposures.6 The link between Parkinson’s disease (PD) and toxicant exposures is well established.7 The link between heavy metals and multiple sclerosis (MS) is also highly suggestive.8 Environmental exposures have been implicated in amyotrophic lateral sclerosis (ALS).9,10 This certainly doesn’t mean everyone that has been exposed to an inordinate amount of toxicants will develop ND. Genetic vulnerability is always at play. The very apt saying applies: “Genetics loads the gun and environment pulls the trigger.”
Next, I run blood tests for “acute” heavy metal11 exposures and urine tests for more “chronic” heavy metal exposures. The technical definition of acute really means being exposed to large amounts of heavy metals at one time, or on a routine or daily basis.12 In the United States, the Agency for Toxic Substances and Disease Registry helps define these guidelines of acute exposures.13 Albeit there are clear clinical guidelines for treating acute heavy metal poisoning, no such guidelines exist for chronic exposure, regardless of the source. This can make not only testing difficult to interpret, but treatment is poorly defined to remove “suspected” heavy metals from the blood, organs, and even the brain.
I compare the patients’ results to those of the CDC’s National Report on Human Exposure to Environmental Chemicals.16 This data is updated one to two times per year. For my patients in the 80th percentile or above, I treat. I do this mostly through sweat depuration,17 exercise to tolerance, high fiber diets18 to reduce enterohepatic redistribution, glutathione,19 alpha lipoic acid,20 N-acetylcysteine (NAC),21 vitamin C,22 probiotics23,24 and occasionally, if body burden is very high, oral heavy metal chelators.25
I also run a battery of tests that reveal the status of key vitamins, minerals, and hormones, as well as assess markers of inflammation. That includes iron levels,26 thyroid function (thyroid stimulating hormone [TSH], free thyroxine [FT4], and free triiodothyronine [FT3]), methylmalonic acid levels (MMA, a more sensitive indicator of B12 status than serum B1227), vitamin E28 homocysteine,29 dehydroepiandrosterone sulfate (DHEA-S),30 pregnenolone,31 testosterone,32 estrogen,33 and many more.
I will consider tick-borne illnesses and viral41,42 insults -- particularly if extreme fatigue is present. I run quantitative titers of Epstein Barr virus (EBV), Cytomegalovirus (CMV) and herpes simplex 6 (HSV-6). If symptoms or history are suggestive, I also include testing for Helicobacter pylori43,44 as its eradication has shown improvements in ND and dementia patients. In addition, stool microbiology cultures for assessment of the gastrointestinal (GI) microbiome45 can also be very helpful. All these can give me a picture of potential infectious load which can activate the immune system and contribute to chronic inappropriate inflammation.
Diet is Key
I recommend all my ND patients go on a gluten-free, anti-inflammatory diet, which includes lots of low glycemic organic fruits and vegetables, such as blueberries, apples, pears, Brussel sprouts and asparagus. I recommend this diet because studies show that the inherently anti- inflammatory Mediterranean diet can improve white matter lesions.46 I ask my patients to remove gluten from their diet, regardless of celiac disease, or sensitivity to gluten, because for some individuals gluten is pro- inflammatory, and even in my patients with negative serology and genetic tests for celiac, I see improvement after they remove gluten — some notice it within a few weeks, some within a few months.
I also suggest that they drink as much organic green tea47 as they can, as polyphenols have been shown to be helpful in neurodegenerative diseases.48 Decaf is fine, as with some individuals, caffeine may worsen their symptoms.
Nutrients I Use in Clinical Practice
Note the large dosage ranges, due to each patient’s uniqueness, some may not tolerate higher doses. For simplicity, I am also only providing daily oral doses, not intramuscular or intravenous.
• NAC54 600-1200 mg
• Acetyl-Glutathione55 400-1000 mg
• Alpha Lipoic Acid (ALA)56 300-1200 mg
• Coenzyme Q1057 400-800 mg
• Acetyl-l-carnitine58 500-3000 mg
• Biotin59 200-300 mg
• Citicoline60 500-3000 mg
• B12 (as methyl, adenosyl and hydroxocobalamin)61,62 1000-5000 mcg
• Lipid Replacement Therapy63 3000-6000 mg
• Omega 3 & 6 essential fatty acids64 2000-6000 mg EPA/DHA, 600-1000 mg GLA
• Whole Coffee Fruit: 200 mg
Botanicals (short list)
• Curcuma longa65 1000-5000 mg, depending on the form
• Mucuna pruriens66 400-1000 mg, standardized to 15% L-Dopa (caution with those on L-Dopa agonist medications)
• Bacopa monnieri67 150-500 mg
• Hericium erinaceus68,69 500-3000 mg
• Low Dose Naltrexone70 1.5-4.5 mg
This information is not a complete list, but more of an idea-starter of how to help patients with these truly devastating conditions.
Dr. Born is co-owner and medical director of Born Naturopathic Associates, Inc., in Alameda, California. He is also a product manager, head of new product development, and scientific advisor for a physician supplement company and is the editor-in-chief of the company’s Focus newsletter.
Dr. Born is a regular speaker at the Annual Restorative Medicine Conference.
1 Chaudhuri A. Multiple sclerosis is primarily a neurodegenerative disease. J Neural Transm (Vienna). 2013 Oct;120(10):1463-6.
2 Reichling DB, Levine JD. Pain and death: neurodegenerative disease mechanisms in the nociceptor. Ann Neurol. 2011 Jan;69(1):13-21. PMID: 21280072
3 What is Neurodegenerative Disease? JPND Research. http://www.neurodegenerationresearch. eu/about/what/. Accessed 28 September 2016.
4 Uttara B, Singh AV, Zamboni P, et al. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009 Mar;7(1):
65-74. PMID: 19721819
5 Johri A, Beal MF. Mitochondrial dysfunction in neurodegenerative diseases. J Pharmacol Exp Ther. 2012 Sep;342(3):619-30.
6 Cannon JR, Greenamyre JT. The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol Sci. 2011 Dec;124(2):225-50. PMID: 21914720
7 Parkinson’s Disease Foundation. Environmental Factors and Parkinson’s: What Have We Learned? 2011. http://www.pdf.org/environment_
parkinsons_tanner. Accessed 28 September 2016.
8 Etemadifar M, Mehrabi B, Kiani-Peykani R, Abtahi SH, Nekouie-Isfahani K, Ramagopalan SV, Fereidan-Esfahani M. Soil heavy metals are associated with the distribution of multiple sclerosis in Isfahan, Iran. Acta Neurol Scand. 2016 Oct;134(4):292-9.
9 Oskarsson B, Horton DK, Mitsumoto H.Potential Environmental Factors in Amyotrophic Lateral Sclerosis. Neurol Clin. 2015 Nov;33(4):877-88. PMID: 26515627
10 Cavaleri F. Review of Amyotrophic Lateral Sclerosis, Parkinson’s and Alzheimer’s diseases helps further define pathology of the novel paradigm for Alzheimer’s with heavy metals as primary disease cause. Med Hypotheses. 2015 Dec;85(6):779-90. PMID: 26604027
11 Chen P, Miah MR, Aschner M. Metals and Neurodegeneration. F1000Res. 2016 Mar 17;5. pii: F1000 Faculty Rev-366.
12 Heavy metals and your health: Frequently asked questions about testing, treatment and prevention. OR Public Health Division. 2016. https://public.health.oregon.gov/HealthyEnvironments/HealthyNeighborhoods/ LeadPoisoning/MedicalProvidersLaboratories/ Documents/HeavyMetals.pdf.
13 https://www.atsdr.cdc.gov/substances/ index.asp
14 http://www.clinicaleducation.org/documents/ standardcareguidelinesforhmtoxicity.pdf
15 https://www.ncbi.nlm.nih.gov/ pubmed/22489724
17 Sears ME, Kerr KJ, Bray RI. Arsenic, cadmium, lead, and mercury in sweat: a systematic review. J Environ Public Health. 2012;2012:184745.
18 Dietary fibres and heavy metal retention in the rat. Environ Res. 1987 Feb;42(1):166-75.
19 Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. PMID:12495372.
21 Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998 Apr;3(2):114-27. PMID: 9577247.
22 Dawson EB, et al. The effect of ascorbic acid supplementation on the blood lead levels of smokers. J Am Coll Nutr. 1999 Apr;18(2):166-70. PMID: 10204833.
23 Ibrahim F, Halttunen T, Tahvonen R et al. Probiotic bacteria as potential detoxification tools: assessing their heavy metal binding isotherms. Can J Microbiol. 2006 Sep;52(9):877-85.
24 Halttunen T1, Collado MC, El-Nezami H, et al. Combining strains of lactic acid bacteria may reduce their toxin and heavy metal removal efficiency from aqueous solution. Lett Appl Microbiol. 2008 Feb;46(2):160-5. Epub 2007
25 Sears ME. Chelation: harnessing and enhancing heavy metal detoxification--a review. ScientificWorldJournal. 2013 Apr 18;2013:219840.
27 Vitamin B12 Assay, Serum. Mayo Medical Laboratories. http://www. mayomedicallaboratories.com/test-catalog/ Clinical+and+Interpretive/9154.
28 Muller DP. Vitamin E and neurological function. Mol Nutr Food Res. 2010 May;54(5):710-8.
29 Herrmann W, Obeid R. Homocysteine: a biomarker in neurodegenerative diseases. Clin Chem Lab Med. 2011 Mar;49(3):435-41.
30 Lapchak PA, Araujo DM. Preclinical development of neurosteroids as neuroprotective agents for the treatment of neurodegenerative diseases. Int Rev Neurobiol. 2001;46:379-97.
31 Baulieu EE. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog Horm Res. 1997;5:21-32. PMID: 9238846
32 Gold SM, Voskuhl RR. Testosterone replacement therapy for the treatment of neurological and neuropsychiatric disorders. Curr Opin Investig Drugs. 2006 Jul;7(7):625-30. PMID: 16869115.
33 Gandy S. Estrogen and neurodegeneration. Neurochem Res. 2003 Jul;28(7):1003-8.
34 Fernandes de Abreu DA, Eyles D, Féron F. Vitamin D, a neuro- immunomodulator: implications for
neurodegenerative and autoimmune diseases. Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S265-77. PMID: 19545951.
35 Schilling S, Tzourio C, Dufouil C, et al. Plasma lipids and cerebral small vessel disease. Neurology. 2014 Nov 11;83(20):1844-52.
36 Elias PK, Elias MF, D’Agostino RB, et al. Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosom Med. 2005 Jan-Feb;67(1):24-30. PMID: 15673620.
37 Yadav RS, Tiwari NK. Lipid integration in neurodegeneration: an overview of Alzheimer’s disease. Mol Neurobiol. 2014 Aug;50(1):168-76. PMID: 24590317.
38 hen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases (Review). Mol Med Rep. 2016 apr;13(4):3391-6.
39 Goncharov NP, Katsia GV. [Neurosteroid dehydroepiandrosterone and brain function]. [Article in Russian]. Fiziol Cheloveka. 2013 Nov-Dec;39(6):120-8. PMID:25509179.
40 Ferri C and Fioranelli M (2014) The Role of Pregnenolone in Inflammatory Degenerative Brain Disease. Interdiscip J Microinflammation 1:121
41 Hernán MA, Zhang SM, Lipworth L, et al. Multiple sclerosis and age at infection with common viruses. Epidemiology. 2001;12(3): 301-306. PMID: 11337603.
42 Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology. 2010 Feb;129(2):154-69.
43 Alvarez-Arellano L, Maldonado-Bernal C. Helicobacter pylori and neurological diseases: Married by the laws of inflammation. World J Gastrointest Pathophysiol. 2014 Nov 15;5(4):400-4. PMID: 25400983.
44 Chang YP, Chiu GF, Kuo FC. Eradication of Helicobacter pylori Is Associated with the Progression of Dementia: A Population-Based Study. Gastroenterol Res Pract. 2013;2013:175729. PMID: 24371435.
45 Smith PA. The tantalizing links between gut microbes and the brain. Nature. 2015 Oct 15;526(7573):312-4. PMID: 26469024.
46 Gardener H, Scarmeas N, Gu Y, Boden-Albala B, et al. Mediterranean diet and white matter hyperintensity volume in the Northern Manhattan Study. Arch Neurol. 2012 Feb;69(2):251-6.
47 Mandel SA, Amit T, Weinreb O, Youdim MB. Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimers Dis. 2011;25(2):187-208. PMID: 21368374.
48 Sarkar S, Mazumder S, Saha SJ, Bandyopadhyay U. Management of Inflammation by Natural Polyphenols: A Comprehensive Mechanistic Update. Curr Med Chem. 2016 May 27;23(16):1657- 95. PMID: 27087243
54 Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav. 2014 Mar;4(2):108-22. PMID: 24683506
55 Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death.
Brain Res Brain Res Rev. 1997 Dec;25(3):335-58. PMID: 9495562.
56 Moreira PI, Zhu X, Wang X, et al. Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta. 2010 Jan;1802(1):212-20. PMID: 19853657.
57 Mancuso M, Orsucci D, Volpi L, et al. Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets. 2010 Jan;11(1):111-21. PMID: 20017723.
58 Calvani M, Carta A, Caruso G, et al. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer’s disease. Ann N Y Acad Sci. 1992 Nov 21;663:483-6. PMID: 1482095.
59 Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: A pilot study. Mult Scler Relat Disord. 2015 Mar;4(2):159-69. PMID: 25787192.
60 Qureshi I. and Endres JR. Citicoline:A Novel Therapeutic Agent with Neuroprotective, Neuromodulatory, and Neuroregenerative Properties. NMJ. June 2010 Vol. 2 Issue 6.
61 Gröber U, Kisters K, Schmidt J. Neuroenhancement with vitamin B12- underestimated neurological significance. Nutrients. 2013 Dec 12;5(12):5031-45.
62 Izumi Y, Kaji R. [Clinical trials of ultra-high- dose methylcobalamin in ALS]. Brain Nerve. 2007 Oct;59(10):1141-7. PMID: 17969354.
63 Nicolson GL. Ash ME. Lipid Replacement Therapy: a natural medicine approach to replacing damaged lipids in cellular membranes and organelles and restoring function. Biochim Biophys Acta. 2014 Jun;1838(6):1657-79.
64 Mehta LR, Dworkin RH, Schwid SR. Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis.
Nat Clin Pract Neurol. 2009 Feb;5(2):82-92. PMID: 19194388.
65 Kim DS, Kim JY, Han Y. Curcuminoids in neurodegenerative diseases. Recent Pat CNS Drug Discov. 2012 Dec;7(3):184-204.
66 Houghton PJ and Howes M-JR. The search for plants to manage neurodegenerative diseases.Ethnopharmacology-Vol III. Year unknown. http:// www.eolss.net/sample-chapters/c03/e6-79-17.pdf. Accessed 30 September 2016.
67 Simpson T, Pase M, Stough C. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain. Evid Based Complement Alternat Med. 2015;2015:615384. PMID: 26413126.
68 Friedman M. Chemistry, Nutrition, and Health- Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds. J Agric Food Chem. 2015 Aug 19;63(32):7108-23. PMID: 26244378.
69 Khan MA, Tania M, Liu R, Rahman MM. Hericium erinaceus: an edible mushroom with medicinal values. J Complement Integr Med. 2013 May 24;10. PMID: 23735479.
70 http://www.ldnresearchtrust.org/content/ldn-and-ms. Accessed 30 September 2016.