Medical Foods Hold Promise In Chronic Pain Patients – Practical Pain Management – By Michael J. Brennan, MD, Steve H. Yoon, MD and Todd Lininger, MD – Sept 2016
Despite the inherent differences in patient populations and their pathologies, there are common approaches to the medical management of chronic pain
The clinician’s goal is to maximize the patient’s functionality by enhancing the analgesic response, and to minimize treatment-related side effects or toxicities.
For the right patients, incorporating an inherently safe option with documented efficacy—like medical foods—into a regimen that includes active exercises, nonopioid and minimal opioid analgesic therapies, and cognitive and behavioral approaches can offer the most effective approach to pain of numerous etiologies.
Adding medical foods into the pain management mix may enhance the ability to maintain or promote analgesia, reduce analgesic doses, and likely lessen actual and potential toxicities of analgesic and coanalgesic agents.
Limitations of Current Analgesic Therapies
NSAIDs are commonly prescribed, but their analgesic efficacy is often modest and comes with a number of serious adverse effects.
The most frequent NSAID-related adverse effects are within the gastrointestinal (GI) tract, including ulceration, gastritis, and gastroesophageal reflux.
It has been estimated that
NSAID-related GI bleeding is responsible for
100,000 hospitalizations and
16,500 deaths per year.
NSAID-induced adverse events are dose-related, and elderly patients are at highest risk for these outcomes. As a result of these risks, the American Geriatrics Society recommends that NSAIDs be restricted, or even eliminated, in individuals older than 65 years.
Yet, older people will also have more pain and the CDC recommends that NSAIDs be used instead of opioids.
The CDC is behind the curve when it comes to biological research and medical progress.
Acetaminophen is another medication commonly relied on to manage chronic pain, but its efficacy is questionable, and it is associated with significant risk of adverse events.
there was high-quality evidence of no benefit for acetaminophen (4 g per day) over placebo for reducing pain intensity at any time over 12 weeks of treatment.
Yes, you read this correctly: high-quality evidence for no benefit, yet this drug is pushed on us repeatedly in most over the counter medications plus our prescription pain medications, like Vicodin or Norco.
The review also found that acetaminophen had no beneficial effect on quality of life, function, global impression of recovery, or sleep quality, at any time point
The poor efficacy of acetaminophen, combined with the risk of severe liver toxicity, presents sufficient doubt about the near-universal reliance on this class of medications for the treatment of chronic low back pain.
Medical foods fall into a distinct FDA regulatory category that differs from both pharmaceutical agents and dietary supplements.
Medical food is defined by the FDA as
“a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.”
The FDA identifies that medical foods are intended for specific dietary requirements of a condition, and
“are specifically formulated and processed (as opposed to naturally occurring foodstuff) for a patient who requires use of the product as a major component of a disease or condition’s specific dietary management.”
With regard to pain, medical foods are intended to meet the potential needs of unique nutritional requirements, resulting from a specific disease or condition as determined by medical evaluation.
Medical foods must be prescribed by a physician after a diagnosis has been made, yet they are not regulated as drugs, and are not subject to any regulatory requirements that specifically apply to drugs.
They are also exempt from food labeling requirements pertaining to health claims under the Nutritional Labeling Act.
Because of their positive safety profile, medical foods may help minimize the number of the concerns typically associated with conventional analgesics.
The rationale for using medical foods in the treatment of chronic pain syndromes arises from an understanding that the metabolic process is disrupted, leading to a depletion of neurotransmitters and an associated synaptic fatigue that results from an increase in precursor turnover and dietary deficiency of the precursors.
A number of neurotransmitters are involved in the modulation and sensation of pain, particularly in conditions such as sleep dysfunction, mood disorders, and fatigue (Table 2).
Abnormalities in neurotransmitter levels also have been documented in fibromyalgia.
Two randomized double-blind studies have evaluated an amino acid formulation (AAF) that contains the neurotransmitter precursors
- serine, and
- arginine (Theramine, Targeted Medical Pharma LLC).
This AAF formulation has been developed as a medical food for the dietary modulation of the metabolic processes associated with pain and inflammation.
These studies demonstrated that the AAF is both safe and more effective than low-dose NSAIDs for the treatment of low back pain.
In 1 study, 129 adult patients with back pain lasting more than 6 weeks were randomized to 1 of 3 groups for 28 days:
- naproxen only (250 mg/day),
- AAF only (2 capsules twice daily), or
- an AAF/naproxen combination.
The goal of medical foods is to restore the homeostasis of these neurotransmitter levels.4,19 Thus, medical foods that correct nutritional deficiencies may be an appropriate target for patients who experience poorly managed pain.
The primary efficacy endpoint of these studies was the change in participants’ awakening stiffness and pain scores
Those receiving AAF alone achieved a statistically significant reduction from baseline in the Oswestry Disability Index (−33%) and Roland-Morris Lower Back Pain Scale (−44%) compared to no change for those receiving naproxen only.
Those in the AAF/naproxen combination group achieved even greater reductions in these pain indices (−60% and −65%, respectively).
All treatments were well tolerated with no adverse events reported; however,
- those in the naproxen-only group experienced significant increases in hepatic transaminases (ALT, AST), indicative of hepatocellular inflammation,
- while those in the AAF or AAF/naproxen groups had no significant increase.
This seems to show that these medical foods can also mitigate the damage from NSAIDs or other pain-relievers.
This incidental finding could be the most important of all. If any neurotransmitter deficiencies (which could lead to hyperalgesia) resulting from opioids can be corrected by these supplements, then it would make sense to add these to opioid therapy.
Comparable results were seen in a similarly designed study, involving 122 patients with chronic back pain who were randomized to 1 of 3 groups:
- ibuprofen alone (400 mg/day),
- AAF alone, or
- a combination of the 2 for 28 days
Patients receiving AAF or AAF/ibuprofen achieved significantly greater reductions from baseline to day 28.
Notably, this study also documented that amino acid precursor levels were more than 2 standard deviations (SDs) below the mean for normal subjects at baseline.
Here we see how long running chronic pain depletes the precursors needed for the body’s own pain relieving mechanisms.
Measurements over the 4-week study showed that treatment with AAF was associated with a significant increase in these precursors.
Overall, these results suggest that AAF, alone or in combination with low-dose NSAIDs, restores plasma amino acid levels and produces measurable improvements in pain as well as demonstrated decreases in inflammation.
A double-blind, placebo-controlled trial in 111 adult patients with a history of sleep disturbance evaluated the effect of another AAF-containing acetylcholine and serotonin precursors (Sentra PM, Physician Therapeutics) on sleep parameters.
those receiving AAF and AAF/trazodone experienced a 3.86- and 6.48-point improvement, respectively, in sleep quality (10-point scale) and a 41- and 56-minute reduction in sleep latency compared to no improvement for either parameter in the trazodone and placebo groups (P<0.001 for both).
Medical Foods in Perspective
Medical foods provide a new alternative to traditional medication therapies.
The GRAS ingredients of medical foods present no concerns for drug interactions and no risk of long-term complications
This seems to be a completely unfounded statement since there are no studies of how these supplements might also disturb the body’s balance of materials.
No inputs to the body have zero effects or results. There are always some side-effects, and some of them can be deleterious, especially in the long run.
I’m surprised anyone with a medical degree would presume to know that this particular addition to the diet will have absolutely no undesired effects, even in the long run.
In addition, because medical foods have a unique mechanism of action (ie, replacement of amino acids that are essential for the synthesis of neurotransmitters responsible for transmitting pain signals and mediating their perception), medical foods may also be used in combination with traditional pharmaceuticals, producing enhanced efficacy and the potential to reduce the dose of the concomitant medication.
Relying on medical foods for pain management will maintain efficacy safely, while reducing the risk of adverse events.
This was evidenced in the AAF/NSAID combination trials where the low doses of NSAIDs used in combination with AAF were associated with a low rate of adverse events.
Indeed, while NSAIDs alone were associated with a slight increase in liver transaminases, the AAF/NSAID combination was not
In summary, medical foods have been an underutilized option for the treatment of chronic pain.
Medical foods provide clinicians with a unique therapeutic modality that has the potential to improve patient outcomes by alleviating pain, and at the same time maximize tolerability and safety.