Peripheral neuropathy is a frequent complication for uterine cancer patients secondary to treatment. It can be very debilitating and reduce the quality of life for many women. Although doctors consider this an acceptable side effect in the interest of saving lives, many who experience this complication would not agree. In this post I will discuss this problem in more detail and give you ways to prevent it, treat it and relieve the symptoms so you can get your quality of life back. Stay to the end where I will discuss a commonly recommended antioxidant you should not take.
WHAT IS PERIPHERAL NEUROPATHY
Peripheral neuropathy (PN) is when nerves outside of the brain and spinal cord, especially in the hands and feet, become damaged and don’t function properly. These nerves are responsible for transmitting signals between the brain and the rest of the body, including sensations like touch, pain, temperature and movement.
When these nerves become damaged, it can cause a range of symptoms including shooting, electric shock like pain, stabbing or burning pain, tingling, numbness and weakness. Hypersensitivity and pain from a light touch or mild temperature changes, called allodynia, can occur. Some women lose the ability to do fine motor movements like fastening a button, sewing or playing the piano.
In some cases, autonomic peripheral nerves can be affected causing low blood pressure with changes in posture, constipation and sexual and urinary dysfunctions.
Motor functions can also become impaired causing weakness leading to gait and balance problems and impaired movements. This is less frequent, but patients who develop PN are three times more likely to fall.
Did you know that the common loss of or changes in taste and smell that happen with chemotherapy are a form of PN? This is because chemo can disrupt the nerves involved in transmitting taste and smell signals to the brain.
WHAT ARE THE MAIN CAUSES OF PERIPHERAL NEUROPATHY
The biggest cause of PN in cancer patients is chemotherapy, but radiation therapy can also cause this.
These are called chemotherapy induced peripheral neuropathy (CIPN) and radiation induced peripheral neuropathy (RIPN).
CIPN occurs in 19% to over 85% of patients.
20-80% of patients being treated with platinum based chemotherapies, including carboplatin, cisplatin and oxaliplatin will develop CIPN.
11-87% of patients being treated with taxane based chemo drugs, including paclitaxel and docetaxel will develop CIPN.
Paclitaxel is the biggest culprit when it comes to CIPN and can cause acute neuropathy during or immediately after an infusion. The severity of CIPN is often proportional to the cumulative dose of the drugs. Unfortunately, the two most commonly used drugs to treat uterine cancer are carboplatin and paclitaxel, both of which have a high incidence of CIPN.
Some patients develop PN or have worsening of symptoms after treatment stops. Symptoms may persist for months or even years. In some cases, nerve damage is irreversible, especially with cisplatin.
RIPN is less common (1%), but can be a late side effect, months and even years later.
Other causes of PN include diabetes, injuries (i.e. carpal tunnel), autoimmune disease and infections.
RISK FACTORS FOR CIPN AND RIPN
Some women may be at higher risk for developing peripheral neuropathy.
- Older age
- A history of smoking
- Any neuropathy before beginning treatment
- Impaired kidney function
- Obesity
- Insomnia
- Anxiety and/or depression
- Diabetes
- Having other comorbidities
- Difficulty remembering
- Constipation
- The use of statins
- Drinking alcohol
- Pelvic radiation >50 Gy to the lumbosacral nerve plexus and/or higher amounts per fraction (2.5 Gy)
- Paclitaxel or docetaxel chemotherapy
- Having certain single nucleotide polymorphisms (SNPs) associated with the following genes: GPX7, SOX10, TRPV1, ABCB1 and EPHA genes. Read More
WAYS TO PREVENT PERIPHERAL NEUROPATHY
COLD MITTS AND COLD SOCKS
One of the most common ways to prevent or reduce the severity of CIPN is with the use of cold mitts and cold socks. Cold exposure causes vasoconstriction (blood vessels narrow), which reduces blood flow to the extremities. This reduces the uptake and exposure of the chemo drugs to the nerve tissues, which may help prevent or lessen the severity of nerve damage.
Cold temperatures are also believed to decrease nerve cell metabolism and reduce the production of reactive oxygen species, which can lead to oxidative stress and nerve damage. Cold exposure has anti-inflammatory effects as well.
Studies have shown that the use of cold mitts and socks significantly reduces the incidence and severity of CIPN in patients receiving paclitaxel chemotherapy.
DOSE REDUCTION
If you start to experience CIPN early during your treatment, talk to your oncologist about a dose reduction of the chemo drugs. Many times doctors will do this to try to reduce the severity of CIPN. If it shows up early, it will likely only get worse as you continue treatments due to the cumulative dose of the drugs in the nerve cells and tissues.
VITAMIN D
Did you know that vitamin D insufficiency is a risk factor for developing CIPN from paclitaxel chemotherapy? Read More Most women with uterine cancer have insufficient vitamin D levels. It is so easy to supplement this critical vitamin that there is no reason you shouldn’t. Ask your doctor to check your blood level before beginning treatment. Your vitamin D level should be 80-100mg/dl.
Can Vitamin D Help Prevent Paclitaxel-Induced Peripheral Neuropathy? Read More
MAGNESIUM
Magnesium has been shown to reduce the incidence and severity of CIPN. It does this through several mechanisms. Magnesium is an antagonist of NMDA (N-methyl-D-aspartate) receptors. These receptors are involved in excitotoxicity and CIPN may be exacerbated by excitotoxicity, where excessive nerve stimulation leads to cell injury or death. By blocking the NMDA receptors, magnesium can help prevent this damage.
Magnesium lowers levels of pro-inflammatory cytokines, like TNF-⍺ and IL-6, protecting nerve cells from damage caused by inflammation.
During chemotherapy, excessive calcium influx into nerve cells can occur, leading to injury. Magnesium helps stabilize the cell membranes and regulate the calcium channels reducing the calcium overload in nerve cells. This helps prevent neuropathy.
In this study, they showed that supplementing magnesium, but not calcium, was statistically and significantly associated with a lower prevalence and severity of CIPN. Read More
HOW TO TREAT PERIPHERAL NEUROPATHY
If you already have PN, there are many things you can do to heal.
SUPPLEMENTS
- R-Alpha Lipoid Acid (R-ALA) 150mg 3x/day, some references say 600mg 2x/day. R-ALA is the active form of alpha lipoic acid and is what your body naturally produces. This is the form you want to take. This is the best studied and proven antioxidant for PN and it is found in every cell in the body. It improves the blood flow around the nerves, is anti-inflammatory and rescues nerve cells from mitochondrial toxicity caused by chemo.
- Benfotiamine 100mg – 250mg 2x/day. This is the fat soluble form of thiamine (vitamin B1). It is absorbed more efficiently than thiamine. Benfotiamine is crucial for the production of myelin, the insulation around nerves and it also protects the blood vessels around the nerves. Benfotiamine improves nerve conduction and function and is also anti-inflammatory.
- Acetyl-L-Carnitine 500mg 3x per day. This is an amino acid and antioxidant. It modulates and controls nerve growth factors and neurotransmitters. Many studies show that it alleviates nerve pain and increases vibration perception in the extremities.
These first three supplements when taken together consistently over time can really improve PN. I experienced this first hand and I know other women who have too. I highly recommend using these three supplements as part of your protocol if you have PN. It will not happen overnight. Nerves are slow to heal and it will take time, but be patient. I had neuropathy in my feet and toes and I took these supplements consistently for 3 months and it completely resolved. Don’t give up if you don’t notice improvement quickly.
- Curcumin 600mg 3x per day. Curcumin is a super supplement. Besides being anti-inflammatory and a good antioxidant, this supplement can also improve blood flow and microcirculation around nerve tissues. It has been shown to relieve neuropathic pain and protect nerve cells from degeneration. It modulates nerve signaling and supports the recovery of damaged nerves.
- Omega 3 fatty acids (fish oil) 1000-3000mg per day. Fish oil (not flaxseed or other oils), has tremendous benefits by reducing inflammation, preventing further nerve damage and helping nerves regenerate. It is also known to reduce pain and morbidity associated with PN.
- Lion’s mane mushroom. This special mushroom does a lot. It stimulates the production of nerve growth factor. This is a protein that is essential for the growth, maintenance and survival of nerve cells and the creation of new nerve cells. Lion’s mane has been shown to help with the regeneration and repair of peripheral nerves and slow the progression of PN. In animal studies and small clinical trials, it was shown to improve nerve conduction velocity and also boost cognitive function.
VITAMINS AND MINERALS
- Methylated B-vitamins, especially B12, stimulate the production of myelin, which insulates all our nerve fibers and enhances the speed and efficiency of nerve signal transmission. In addition, B12 is involved in methylation. This is a process that helps regulate levels of homocysteine. High levels of homocysteine are toxic to the nervous system and are associated with PN. B12 converts homocysteine to methionine, which is a non-toxic amino acid that supports nerve health. Low B12, folate and B6 have been linked to PN. Use caution in supplementing B6, as too much can be toxic to nerves. Besides improving nerve function, methylated B vitamins also offer pain relief and relieve inflammation.
- Vitamin D (see above on prevention)
- Magnesium (see above on prevention)
TOPICAL CREAMS AND GELS
These have all been recommended by naturopathic doctors and patients for helping with PN.
- Frankincense essential oil mixed with coconut oil on your feet at night
- Arvesa hemp cream. Contains natural hemp oil, arnica, turmeric, aloe and menthol for pain relief.
- Kunzea pain relief cream. Contains rosemary leaf, tasmanian kunzea oil, tasmanian lavender and vitamin E
- Preparation H cooling gel. Not just for hemorrhoids, it can help relieve burning and itching and sooth the skin. Has aloe vera, vitamin E and witch hazel
- THC pain cream. Has proven benefits for relieving pain
- Capsaicin cream. Higher strengths seem to work better
- BAK gel. A compounded prescription topical pain gel that contains baclofen, amitryptiline and ketamine. It relaxes muscles by blocking nerve receptors
TREATMENTS
- Hyperbaric oxygen therapy (HBOT). HBOT has been shown to improve PN. It bathes the nerve cells and tissues in high doses of oxygen and improves circulation around the nerve tissues. This promotes healing of damaged nerves and nerve regeneration.
- Acupuncture and acupressure (as soon as CIPN starts for best results). Acupuncture involves inserting tiny needles at specific points on the body called acupoints. Acupressure is similar, but instead of needles, it is the application of pressure at the acupoints. It is believed that stimulating specific points on the skin can block pain signals from reaching the brain. Acupuncture can also trigger the release of endorphins and other neurochemicals that act as natural painkillers. It can reduce inflammation by regulating the immune system, reducing pro-inflammatory cytokines. By stimulating blood flow, acupuncture can promote the release of nerve growth factor to regenerate damaged nerves.
Acupuncture for Chemotherapy‐Induced Peripheral Neuropathy in Breast Cancer Survivors: A Randomized Controlled Pilot Trial Read More
- Transcutaneous Electrical Nerve Stimulation (TENS). This is a non-invasive method of relieving pain and it has been used as a treatment for CIPN. Electrodes (patches) are placed on the skin and low-voltage electrical currents are used to stimulate sensory nerves. According to the “gate control theory”, TENS stimulates A-beta fibers, which are large myelinated nerve fibers in the skin and muscles that send signals to the spinal cord. These signals can “close the gate” to pain signals traveling through A-delta and C fibers ( small, unmyelinated nerve fibers), which carry pain information. By stimulating the larger fibers, TENS effectively blocks the pain signals from reaching the brain. TENS units can modulate pain perception, improve nerve function and improve quality of life for those with CIPN.
- Hot and Cold therapy. Heat causes blood vessels to dilate increasing blood flow to the area. Cold causes blood vessels to constrict, reduces inflammation and numbs pain. By alternating between hot and cold, you stimulate a “pumping action” that improves overall circulation. This enhanced circulation can help flush out metabolic waste products and provide better nourishment to the nerves. Also, both heat and cold have pain-relieving properties so alternating between the two may help modulate nerve activity and reduce the sensation of pain.
- Exercise. Exercise may be the last thing you want to do if you have PN in your hands and feet. However, exercise is a proven way to improve nerve function and help relieve pain. Gentle walking, swimming, cycling and balance training are all very beneficial.
- Hand specific exercises include finger taps, finger rolls, ball squeezes (stress ball, tennis ball), grasping exercises, towel scrunching and hand dexterity exercises like opening and closing buttons and zippers.
- Foot specific exercises include ankle rolls, toe raises, heel raises and calf raises. Foot rolls, which is rolling a ball or other object under each foot, toe spreading and walking on uneven surfaces can also help.
Do all of these things with care and mindfulness to prevent injury.
MEDICATIONS
These are all medications that have been used successfully for the treatment of PN. I know many patients who take low-dose naltrexone to prevent cancer recurrence and it can be very effective in treating PN. I will write all about this particular medication in another post. Gabapentin is often prescribed for neuropathic pain and I have used this for back pain with good success.
With the exception of low-dose naltrexone, I recommend trying natural remedies first and only resorting to prescription medications for pain as a last resort as they can have many undesirable side effects.
- Low-dose naltrexone (LDN)
- Gabapentin
- Tricyclic antidepressants
- Pregabalin (Lyrica)
ONE SUPPLEMENT NOT TO TAKE
N-Acetylcysteine or NAC is a supplement commonly recommended by nurses and oncologists to cancer patients to treat or prevent CIPN among other things. Many naturopathic doctors advise against the use of NAC for cancer patients.
NAC is a precursor to glutathione, one of the body’s most powerful antioxidants. In fact, NAC boosts the production of glutathione, replenishing intracellular stores of this antioxidant. Most cancer therapies, pharmaceutical and natural, work in part by depleting glutathione so you don’t want to take something that increases the levels of this in your body.
Glutathione has been shown to reduce the effectiveness of some chemotherapy drugs and other treatments. Glutathione is found at higher levels in cancer cells and it is thought that it acts to intercept and inactivate many chemotherapy agents before they can kill cancer cells. It also protects cancer cells from an iron-dependent form of cell death called ferroptosis and helps cancer cells escape apoptosis (programmed cell death).
NAC may reduce the activity of T-lymphocytes, which are involved in identifying and destroying cancer cells. In fact, some cancers are made stronger and become resistant to multiple chemotherapy drugs with the use of NAC.
I personally do not take this supplement due to the reasons I mentioned above.
Glutathione in cancer progression and chemoresistance: an update Read More
Glutathione Levels in Human Tumors Read More
I pray you never have to deal with PN, but if you do or know someone who is suffering from this, I hope this information helps. Please share with others.
As high as the heavens are above the earth, so great is His love for those who fear Him.
~Psalm 103:11