Neuropathy and MTHFR. Nutritional Treatment for Neuropathy. Dr Neil Rawlins Dr Katie Karlson

Neuropathy and MTHFR Nutritional Treatment for Neuropathy Dr Neil Rawlins Dr Katie Karlson Introduction • Some of this presentation involves comple...
Author: Marybeth Porter
8 downloads 4 Views 11MB Size
Neuropathy and MTHFR Nutritional Treatment for Neuropathy

Dr Neil Rawlins Dr Katie Karlson

Introduction • Some of this presentation involves complex information, and some studies are not as clear as we’d like • However, there is evidence of real and well researched information that may be beneficial to many and with little--if any--harm

Presentation Objectives • Understand nerve pain can be treated with nutritional therapy • The best studied neuropathy is in diabetics, but it has helped in neuropathy from unknown causes • We will describe the proposed cause of diabetic nerve pain and poor wound healing • Understand the potential benefit of a vitamin combination in the management of Diabetic Symptoms

Causes of Neuropathy • • • • • • • • • •

Diabetes Alcohol abuse HIV Thyroid disease B12 and Folate deficiencies (MTHFR gene) Lyme disease Toxins (heavy metal, chemical exposure) Hereditary Idiopathic (We don’t know!) Others

Nutritional therapy •

Nutritional therapy doesn’t replace understanding why you have the neuropathy and treating the underlying cause. You need to have it evaluated to make sure it is not due to one of the treatable causes.



We will show the studies from diabetes since it has the most information.



Not all of the information will be applicable to all causes of neuropathy

MethylTetraHydroFolate (MTHFR) Deficiency • This is new enough research that most physicians are not aware of this information-in the vast sea of information that is available • Thank You Human Genome Project!

This is the pathway (test at the end) You Are Here

The Human Genome Project • The Human Genome project has developed a new approach to medical problems

• There are several of the B vitamins that require activation before they are useful to the body

• It has been found that by taking the active forms of theses vitamins you are able to bypass metabolic glitches and compensate for genetic and environmental problems • Please come to MTHFR talk on October 22 to learn more!

MTHFR Gene •

Not everyone is born equal, as far as methylation is concerned



As much as 70% (in the US) inherit a defective or partially defective gene--this means the key methylating gene, MTHFR, does not work well



There is an increased need for the active forms of B12 and folic acid



If you have this MTHFR defect (and other problems like diabetes) you are more susceptible to nerve and wound complications

Impact of Diabetic Neuropathy • 60-70% of foot ulcers are preceded by neuropathy • 85% of diabetes related lower limb amputations are preceded by a foot ulcer • Most Common Proximate, Nontraumatic Cause of Amputations • Largest number of diabetes related hospital bed-days Frykberg R, et al. Journ of Foot and Ankle Surgery 2006;45(5):S2-S8. Gordois et al. Diabetes Care. 2003;26:1790-1795. Reiber G, et al. Diabetes in America. 1995; 2nd ed:409-428.

Reiber GE, Vilekyte L, Bokyo EJ et al. Diabetes Care.1999;22. Pecoraro RE, Reiber GE, Burgess EM. Diabetes Care. 1990;13.

Diabetic Neuropathy: A Small Fiber Disease Normal Skin Biopsy

Normal innervation with small nerve fibers seen in the epidermis (arrows). Skin biopsy specimens with protein gene product 9.5 immunostaining.

TAVEE J , ZHOU L Cleveland Clinic Journal of Medicine 2009;76:297-305

Small Fiber Neuropathy Biopsy

A specimen from a patient with small fiber neuropathy shows denervation with no small nerve fibers seen in the epidermis

Symptoms and Signs of Diabetic Peripheral Neuropathy Symptoms

Signs

Small Fiber

Large Fiber

• Numbness or loss of feeling (asleep or “bunched up sock under toes” sensation) • Prickling/Tingling • Aching Pain • Burning Pain • Lancinating Pain • Allodynia • Defective Thermal Sensation • Decreased Sweating

• Diminished vibratory perception • Decreased knee and ankle reflexes • Reduced protective sensation such as pressure, hot and cold, pain • Diminished ability to sense position of toes and feet • Pain is deep, aching or cramping

Symptoms and signs progress from distal to proximal over time Boulton AJ, et al. Diabetes Care. 2005 April; 28(4):956-62.

Etiology of Diabetic nerve pain Elevated Glucose Metabolic Abnormalities AGEs´Oxidative Stress´Polyols´EFA

Endothelial (Blood Vessel) Abnormalities µET´µAII´¶NO´¶PGI2

Microvascular Insufficiency

Neuronal and Schwann Cell Dysfunction

Vinik A. The Amer Journal of Med. August 1999

Endothelial Dysfunction in Diabetic nerve pain: ƒ Endothelium (blood vessel wall): a biologically active organ ƒ Deranged nitric oxide pathways ƒ Oxidative stress is probably one of the ways toxins and other metabolic diseases cause neuropathy

Endothelial Dysfunction in the Diabetic Foot A consequence of low nitric oxide levels poor microcirculation loss of protective sensation foot ulceration Diabetic nerve pain

Moncada S., Higgs A.N Engl J Med 1993; 329:2002-2012. Schäffer M, et al. Nitric Oxide Regulates Wound Healing. J Surg Res 1996; 63:237-240. Schwentker A, et al. Nitric Oxide and Wound Repair. Surg Clin N Am 2003; 83:521-530.

Microvascular Damage Leads to DPN Normal nerve

Damaged nerve Damage to myelinated and unmyelinated nerve fibers

Occluded vasa nervorum • Examination of tissues from patients with diabetes reveals capillary damage, including occlusion in the vasa nervorum • Reduced blood supply to the neural tissue results in impairments in nerve signaling that affect both sensory and motor function Dyck PJ, Giannini C. J Neuropathol Exp Neurol. 1996;55:1181-1193. Sheetz MJ, King GL. JAMA. 2002;288:2579-2588.

Association of Metformin and Clinically Worsened Diabetic pain Clinical Markers of Neuropathy Severity

12

Neuropathy Severity

10

Neuropathy Impairment Score

10

8 6 P 6 months of metformin to those without metformin • Results demonstrate that metformin contributes to the severity of DPN (P