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Peripheral neuropathy (or, polyneuropathy) is normally attributed to diabetes, thyroid problems, alcohol abuse, and consistent exposure to chemotherapy treatments. But it can likewise be attributed to the use of drugs other than chemotherapy agents. Notwithstanding multiple statements and advertisements proclaiming that statins are safe and vital to lowering cholesterol and preventing coronary events, contrary evidence exists that long-term exposure to statins may substantially increase the risk of/induce and exacerbate peripheral neuropathy by 15% in the first year and 26% for two or more years (1, 2, 3). Moreover, statins can contribute to suppression of our immune system and activation of helper T-cells (lymphocyctes produced in the thymus gland) (4); likewise statins have been attributed to liver and kidney injury (5), as well as reduction in bone mineral density and resulting osteoporosis (6). Contrary to some studies that report statins as reducing the risks of advanced prostate cancer (7), other peer-reviewed studies question whether long-term use of statins actually cause cancer (8) and report findings that statins do not provide a protection against breast or prostate cancer. (9)

Also, while antiangiogenic (retard blood vessel growth) drugs are in vogue this year (Celebrex/Vioxx, thalidomide) and low-dose frequent chemotherapy is recognized as being both cytotoxic and antiangiogenic, how does the reduced blood vessel formation from the accumulation of these various antiangiogenic agents affect continued health of our nerves? I suggest that long-term use of antiangiogenic agents certainly deny blood supplies to nerves (as well as cancer and healthy tissue) and either alone or combined, certainly induce peripheral neuropathy.

Therefore, while statins are most effective in preventing coronary events, COX-2 inhibitors are essential for pain and antiangiogenesis, and thalidomide might eventually prove to be an effective antiangiogenic agent---I suggest that it is incumbent on us to analyze our own chemical/drug cocktails and combinations in order to optimize the cumulative and combined effects on our quality and length of life---I likewise suggest that in our monthly 15 minute sessions with our doctors, they are not doing so on our behalf.

Many cancer patients are also taking a myriad of other drugs, and most of us take some statin and antiangiogenic agents. Are we thus assuring that we will suffer treatment-limiting and debilitating (and possibly permanent) peripheral neuropathy by taking Lipitor for its cholesterol-lowering effects, Celebrex for pain and antiangiogenesis, blood pressure medicines, and thalidomide for antiangiogenesis (thalidomide is well-known for causing peripheral neuropathy)? When we develop peripheral neuropathy, do our doctors analyze our medication list to assess the individual and cumulative effects of all of our medications? (My question is obviously cynical and rhetorical.)

Many cancer patients who undergo several months of chemotherapy will develop peripheral neuropathy to some extent. The nerve damaging effects of chemotherapy are cumulative and as the chemotherapy treatments are continued, the condition often becomes treatment-limiting and physically debilitating. Medical science does not know of any agent to relieve or delay the onset of peripheral neuropathy and we are often told that "...it is just our old friend Taxotere...", without any analysis of the cumulative antiangiogenic effects of our other drugs as possibly contributing in a major way to our peripheral neuropathy.

The probable side-effect of peripheral neuropathy resulting from long-term chemotherapy is well-known by our oncologists, yet they have no suggestions about how to alleviate it except to reduce the dose of the chemotherapy agent or suspend treatment. In my opinion, our doctors are not comfortable with any agent we can buy in a drug or health food store and often just shrug their shoulders and tell us to try it if we want. Nor do I believe that our doctors are aware of the many side effects (and accumulation thereof) of the many drugs we take to support and augment our cancer treatments or alleviate side-effects there from.

After 17 weekly Taxotere treatments and while I was still responding (I was also taking 400 mg of Celebrex/day + daily Norvasc and Accupril for blood pressure control), I was forced to stop treatment due to extreme peripheral neuropathy and resulting onychosis (10). I wrote about this in Chemotherapy - Part 2. In that paper I suggested Glutamine as a possible agent to relieve or delay peripheral neuropathy. In subsequent chemo treatments I continue with daily Glutamine and believe that it offers some relief; but after 2+ years of chemotherapy, I still suffer considerable peripheral neuropathy. However, below I suggest other possibilities that might partially relieve and/or delay this treatment-limiting side-effect of chemotherapy.

In addition to a mandatory review of every complementary drug we are taking that might have any characteristics of inducing peripheral neuropathy, and optimizing their utilization in view of our own concept of quality/quantity of life---- in SUMMARY, I suggest several possible solutions to alleviate/delay peripheral neuropathy while engaged in our saga of prostate cancer and the treatments therefor---with the exception of shakuyaku-kanzo-to, all of these items are available in a drug/health food store:

1) Glutamine at 10 gm X 4/day as delineated in my above paper.

2) Shakuyaku-kanzo-to (not available in a drug/health food store)---an ancient Chinese/Japanese herbal concoction for muscle spasms and tingling in the hands and feet.

3) Gamma-linolenic acid (GLA), fish oil concentrate, and ascorbyl palmitate --corrects fatty acid imbalance.

4) Vitamin B12 in the form of methylcobalmin (methl B12) + folic acid.

5) Alpha-lipoic acid + acety-L-carnitine + N-acetylcysteine + vitamin C.

(NOTE: we must be cognizant of the fact that the studies/reports of agents effective against peripheral neuropathy state that such agent(s) only delay or partially mitigate peripheral neuropathy---none proclaim to prevent it---so, with our cancer and long-term use of statins, antiangiogenic agents, and chemotherapy, we must accept the fact that we will all suffer peripheral neuropathy to some extent.)

DEFINITIONS

...Neuropathy is the wasting and inflammation of nerve tissues, often manifest in peripheral extremities (hands/feet). Symptoms are burning, shooting pain possibly concurrent with a cold sensation, transient numbness, and weakness of the extremities. The sensation(s) can be transient, moving from finger to finger/toe to toe, and radiating up the arm or leg. Symptoms usually improve upon stopping the drug, although improvement can take 6-8 weeks and pain can worsen before it improves. Neuropathy is commonly caused by diabetes, fatty acid imbalance, restriction of blood supply to nerves (could COX-2 inhibitors add to the condition?), nutritional deficiencies, and chemotherapy agents. (11) If peripheral neuropathy is bilateral, drug induction is usually attributed thereto----but if it is unilateral, there are possibly other non-drug related problems.

...gamma-linolenic acid (GLA)--known as "the good omega-6" fat; regulates metabolic processes down to the cellular level---among several expected effects of GLA: a cytotoxic agent for cancer and an arthritis reliever. (12).

...ascorbyl palmitate--fat-soluble form of ascorbic acid (vitamin C); unlike ascorbic acid, which is water soluble, ascorbyl palmitate is stored in cell membranes until needed by the body; free-radical antioxidant. (13)

...folic acid/folate (vitamin B9)---water-soluble and important in red blood cell formation, protein metabolism, growth and cell division. (14)

...alpha-lipoic acid (ALC)---serves as a coenzyme in the Krebs cycle and in the production of cellular energy---possibly the "perfect and ideal" antioxidant---in Germany it is an approved treatment for peripheral neuropathy; in the US it is sold as a dietary supplement, usually in 50 mg tablets. (15)

...N-acetylcysteine (NAC)---promotes detoxification and acts directly as a free radical scavenger---protects normal cells, but not malignant cells, from the toxic effects of chemotherapeutic agents and radiation---can reduce tumor formation and prevent metastases, but does not interfere with cytotoxicity of chemo agents. (16)

...acetyl-L-carnitine (ALC) --modulates cellular functions, including the transfer of fatty acids for energy production---restores nerve growth factor function---neuropathies respond to ALC (17)---daily administration of ALC during Taxol treatment completely prevents occurrence of neuropathy and myelosuppression (18)---it is associated with increased nerve conduction velocity; in a trial it prevented 73% of nerve conduction defects and promoted/accelerated nerve-fiber regeneration. (11, pp. 476)

...vitamin B12---the common form of vitamin B12 found in the drugstore is cyanocobalamin (cyano B12), but this form of B12 is inferior to methylcobalamin (methyl B12) as an antioxidant---look on your B12 bottle to see which form of the vitamin you have; and assure that you are taking the methyl form---studies have shown that methl B12 provides protection from neurotoxicity and is neurotrophic (promotes growth of nerve cells), which may help regenerate peripheral nerve damage (19)---methl B12 should be taken sublingual (under the tongue).

...shakuyaku-kanzo-to (TJ-68) is an ancient oriental herbal concoction used for many ailments, including acute muscle spasms, tingling hands/feet, and peripheral neuropathy---it is a blend of two crude drugs: shakuyaku (peony root) and kanzo (glycyrrhiza root) (20)---(note: these were among the ingredients of PC SPES)---the herb is manufactured as prescription only in Japan by Tsumura; their contact in the US is 949-833-7882---likewise, some men have found the herbal mix at the Academy of Oriental Medicine (512-323-6720) and New Breeze (Ken Morehead--919-384-1437, or kfmk@aol.com). Shakutaku-Kanzo-to has been reported as effectively reducing the severity of peripheral neuropathy, arthralgia (joint pain), and myalgia (muscular pain) in Taxol/Carboplatin protocols. (21)

...statins = agents capable of accelerating the rate of secretion of a given hormone by the anterior pituitary gland--- cholesterol-lowering medications known as reductase inhibitors (inhibitors of enzymes) offering up to 37% reduction in the risk of coronary events (22, 23)---estimates are that half of the US population will shortly be taking a statin drug (24)--common statins are Lipitor, Zocar, Pravachol, Lescol, and Mevacor (25).

1) Glutamine @ 10 gm (about one heaping teaspoon) X 4/day----see Chemotherapy - Part 2 for logic and references.

2) Shakuyaku-kanzo-to @ 2.5 gm X 3/day.

3) Gamma-linolenic acid (GLA) + fish oil concentrate + ascorbyl palmitate**.

4) Vitamin B12 (methylcobalamin) @ 5-40 mg/day sublingual (under the tongue) + 2000-5000 mcg folic acid**.

5) Alpha-lipoic acid @ 250 mg X 2/day + acetyl-L-carnitine @ 1000 mg X 2/day + N-acetylcysteine @ 600 mg X 2/day + 3000 mg vitamin C X 2/day**.

NOTE: I am not a doctor and can not give medical advice. I am not a medical researcher. I am an unemployed prostate cancer patient in my sixth year of this saga and I performed this layman’s analysis for my own edification and decision-making purposes. In conjunction with a competent medical team, every cancer patient must make their own decisions regarding treatment options. I make no claim that this analysis is definitive or complete and I invite any and all competent suggestions/corrections that will provide salient information to prostate cancer patients in our search for methods to extend quality and quantity of life while battling a terminal disease.

(3) Gaist D, et al.; Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?; Eur J clin Pharmacol 2001 Mar;56(12):931-3

(12) http://www.fatsforhealth.com/library/libitems/omega6.php and www.vitacost.com/science/nutrients/gammalinolenic.htm

(17) www.health-pages.com/lc/ ; www.smart-drugs.com/smart/info-ALC.htm