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10 Articles in Volume 9, Issue #9
Neuroethics at the Close of the Decade of Pain Control and Research
Cumulative Response from Cranial Electrotherapy Stimulation (CES) for Chronic Pain
Dextrose Prolotherapy for Unresolved Wrist Pain
Adult Growth Hormone Deficiency in Fibromyalgia
Middle Ear, Eustachian Tube, and Otomandibular/Craniofacial Pain
Computerized Dynamometry in Impairment Evaluations
Co-Morbid States Are the Rule—Not the Exception—in Pain Practice
Nutritional Supplements in Pain Practice
Testosterone Replacement in Female Chronic Pain Patients
A Practical Guide for the Use of Opioids in Chronic Pain

Nutritional Supplements in Pain Practice

Restoring the Natural Opioid System with D-Phenylalanine (DPA)
A Novel Therapeutic Approach

There is hardly a physician in pain practice who doesn’t recommend some type of nutritional supplement for their patients. It may be a vitamin, mineral, herb, amino acid, hormone, fish oil, or other. The problem with nutritional supplements is simply that there are few, if any, evidenced-based studies to support the use of non-prescription supplements. What’s more, there won’t be. There’s simply not enough money to be made in nutritional supplements for any party to undertake such studies. Despite this handicap, we receive numerous inquiries from MDs about the use of nutritional supplements. We want to help, so we will periodically publish articles about a practitioner’s “favorite nutritional therapy.” While we can make no claims of efficacy or safety—nor endorse any supplements—we want to share positive, clinical experiences regarding nutritional supplements. Just make use of these experiences if you believe your patients can benefit.

The body produces its own powerful pain-modulating neurotransmitters. Chronic pain and other chronic stressors, combined with a diet low in protein, can create deficiencies in the three most critical of these pain-modulators: serotonin, gamma-amino-butyric acid (GABA), and endorphin.1-3

In earlier articles in Practical Pain Management, we discussed the use of diet and amino acid supplementation in promoting optimal levels of serotonin and GABA. This article targets the use of diet and amino acids in the optimization of the endogenous opiates, the endorphins—our most potent natural analgesics. Endorphin is a term used to identify a group of naturally-occurring compounds that can powerfully reduce pain.1 Primary among them are the beta-endorphins and the enkephalins. These endogenous opioids, molecule-for-molecule, are thousands of times stronger than morphine.2,3 B-Endorphin is composed of 20 amino acids (see Table 1). Amino acids are the constituents of protein-containing foods.6 There are a total of 22 amino acids found in these foods in varying amounts. If adequate protein is consumed, endorphin levels may remain high enough to effectively modulate pain. Chronic pain sufferers, however, typically become significantly deficient in their endorphin-producing capacity.1-3

The 21st century US diet is often inadequate in protein content. It is also low in the anti-inflammatory vitamin and mineral co-factors which are typically found in fresh vegetables and fruits. Pain and the medications needed for relief can both reduce appetite and further reduce the intake of nutrients vital to the production of endorphins. Since opiate medications depend on endorphin activity to support their effectiveness, supplying the amino acid building blocks for the production of additional endorphins can be critically beneficial.


To raise and sustain endorphin levels, daily protein consumption should be at least 30 grams, three times per day. Pain patients rarely meet these minimal protein requirements. In particular, they skip breakfast and often eat primarily sugars and starches during the remainder of the day. Aggressive counseling may be required to increase a pain patient’s intake of foods that contain significant amounts of protein. Higher quantity is needed post-surgery or post-infection. Providing an amino acid supplement that contains most or all of the 22 amino acids—including the nine essential amino acids—can be very helpful. Finally, the therapeutic use of particular amino acids in supplement form can often provide surprisingly quick and dramatic improvements in pain relief.

Use of D-Phenylalanine to Raise Endorphins

The amino acid d-phenylalanine (DPA) slows the action of the enzymes—particularly carboxypeptidase A or endorphinase and enkephalinase—that degrade the endorphins.4-7 The enzymatic degradation of endorphins and enkepinalins is a constant, somewhat indiscriminate, process. Slowing down this endorphin-reducing mechanism can diminish pain within twenty-four hours. In our clinic, we have seen pain relief occur within ten minutes after the ingestion of as little as 500mg of DPA. Our usual dose in chronic pan patients is 500-2000mg of d-phenylalanine, two to four times a day.

D-phenylalanine’s endorphin-protective properties were researched and confirmed in the 1980s in trials conducted at the Chicago Medical School by pharmacology professor Seymour Ehrenpreis, PhD.4,5 Dr. Ehrenpreis was motivated by the urgent need to assist the medical staff in reducing the doses of opiate medications used in their hospital. He, and subsequently several other researchers, have confirmed the usefulness of this benign amino acid in acute as well as chronic pain management.6,7 Still other researchers have combined DPA with acupuncture with additional benefit.

Relationship of D- And L-Phenylalanine

DPA, a non-nutritive amino acid is available alone or bound to l-phenylalanine (LPA) as DLPA. LPA is an essential amino acid used by the body to create a number of vital compounds, including l-dopa, dopamine, norepinephrine, adrenalin, and thyroid hormone. DPA has twice the endorphinase inhibitory effect of DLPA, while DLPA is more energizing and more readily available in health food stores, pharmacies, and online. For anxious or agitated patients, DLPA can sometimes be experienced as overly stimulating, while more mood-stable patients find it to be both pain-relieving and energy-enhancing. Our recommended DLPA dose is: 1000-2000mg, three times a day. I recommend that patients with malignant melanoma, extremely high blood pressure, Grave’s disease, constant migraine, or phenylketonuria avoid DLPA.

Clinical Experience

Our outpatient clinic has used both DPA and DLPA successfully since 1990, as have other practitioners. Paul Anderson, MD, a pain specialist and CEO of Natural Pain Relief Center, and former president of the Canadian Institute of Biomechanics, has been experimenting with alternative pain management methods for many years. He has found DPA to be very effective when combined with a high protein/high vegetable diet. He’s also found that low levels of microelectric current can initially amplify the effects of the nutrients. His results: “93.1% of my patients using a combination of electromagnetic current, proper diet, nutritional supplements with amino acids and meditation/relaxation experienced significant long-lasting chronic pain relief without any pain medication. Most patients took a minimum of 1000mg of DPA four times a day initially and didn’t require it for pain control after 14 days.”

Table 1. ß-Endorphin and ACTH 20-chain Amino Acid Compositions




Laboratory and clinical reports indicate that DPA may reduce pain by inhibiting the enzymatic degradation of endorphin and enkephalin. This is an inexpensive therapy that can be used for acute or chronic pain and can be used as an ancillary treatment to opioids and other measures.

Milk Thistle to Enhance Liver Function and Drug Therapy
Utilizing milk thistle to detoxify a liver may maximize pain relief by reducing the challenge to a chronic pain patient’s liver attempting to metabolize an opioid and adjunctive medication regimen.
Donald Adema, DO

Pain management strategies are sometimes ineffective because of liver congestion, fatty liver, or other dysfunction which challenges the “bio-availability” pathways of liver metabolism. Clinical experience is continuing to reveal enhanced therapeutic success when liver function is ensured or enhanced. The following is a brief clinical recommendation. My experience indicates that milk thistle assists liver metabolism and boosts pain and palliative care.

The Clinical Problem

As an initial history is obtained, warning signs of prior drug abuse, liver disease or long term multi-medication use should alert the practitioner to a potential liver challenge to pain and palliative therapy. The nausea secondary to the liver congestion of a fatty liver will often compromise consistent medication delivery. In some cases, a fatty liver may almost totally prohibit normal drug metabolism. The new concept of a “leaky gut” may also contribute to incomplete digestion, poor absorption and an overburdened and toxic liver. Inadequate water intake or over-ingestion of dehydrating fluids such as iced tea or sodas may also lead to poor digestion and sluggish and congested circulation. Dehydration, when coupled with a fatty liver, may lead to portal hypertension which can certainly hamper pain palliation. The major detoxifying and metabolic organ of the body must be at its best to maximize pain and palliative efforts.

Clinical Experience and Recommendations

For some time, many liver transplant teams—such as the one at University of California, San Diego—have utilized milk thistle to detoxify a liver that is required to meet the challenges of host versus graft responses and the myriad of medications involved in transplantation. I routinely use it in pain and palliative care patients as well.

I often add glutathione to provide cleansing and repair of the gastrointestinal tract. I find these supplements often reduce the opioid dosage or make the current dosage more effective.

Water intake is paramount in any liver support effort. The recommended six to eight glasses of eight ounces of water a day initiates a cleansing effort in all patients. A reduction in sodas, sweetened juices, caffeinated beverages and dairy products also lowers the challenge to a liver attempting to metabolize an opioid and adjunctive medication regimen.


To maximize palliative, pain, or hospice care, the physiological activity of the liver should be at its best. Liver transplant teams, hospice teams and increasing numbers of practitioners, including myself, are implementing liver health and enhancement protocols. Life style changes, accompanied with a simple addition of milk thistle, can often be an achievable and successful effort.

Last updated on: December 20, 2011
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