Three double-blind trials have investigated the effects of supplementing a combination of the enzymes trypsin and chymotrypsin for seven to ten days on severe low back pain with or without accompanying leg pain. Eight tablets per day were given initially in all trials, but in two trials the number of pills was reduced to four per day after two to three days.

One of these trials reported small, though statistically significant improvements, for some measures in people with degenerative arthritis of the lower spine.People with sciatica-type leg pain had significant improvement in several measures in one trial, while another found the enzymes were not much more effective than a placebo. These trials included chronic low back conditions, so their relevance to acute LBP alone may be limited.

Several animal studies and some research involving humans suggest that a synthetic version of the natural amino acid phenylalanine called D-phenylalaline (DPA), reduces pain by decreasing the enzyme that breaks down endorphins. It is less clear whether DPA may help people with LBP, though there are a small number of reports to that effect, including one uncontrolled report of 27 of 37 people with LBP experiencing “good to excellent relief.” In a double-blind trial, University of Texas researchers found that 250 mg of DPA four times per day for four weeks was no more effective than placebo for 30 people with various types of chronic pain; 13 of these people had low back pain. In a Japanese clinical trial, 4 grams of DPA per day was given to people with chronic low back pain half an hour before they received acupuncture. Although not statistically significant, the results were good or excellent for 18 of the 30. The most common supplemental form of phenylalanine is D,L-phenylalanine (DLPA). Doctors typically recommend 1,500–2,500 mg per day of DLPA.

A combination of vitamin B1, vitamin B6, and vitamin B12 has proved useful for preventing a relapse of a common type of back pain linked to vertebral syndromes, as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials. Typical amounts used have been 50–100 mg each of vitamins B1 and B6, and 250–500 mcg of vitamin B12, all taken three times per day. Such high amounts of vitamin B6 require supervision by a doctor.

Proteolytic enzymes, including bromelain, papain, trypsin, and chymotrypsin, may be helpful in healing minor injuries because they have anti-inflammatory activity and are capable of being absorbed from the gastrointestinal tract. Several preliminary trials have reported reduced pain and swelling, and/or faster healing in people with a variety of conditions who use either bromelain or papain.

A preliminary report in 1964 suggested that 500–1,000 mg per day of vitamin C helped many people avoid surgery for their disc-related low back pain. No controlled research has been done to examine this claim further.