What to Combine L-Ornithine With

L-ornithine most often enters an athlete's diet as part of complexes. The editorial team examined which supplements it makes biochemical sense to combine it with, which combinations lack evidence, and which are better avoided.

Are combinations needed at all

L-ornithine is rarely sold as a single component: it can often be seen as part of pre-workout complexes, «nitrogen boosters», sleep aids, and «liver support» products. This creates the impression that ornithine works more strongly in combinations. In reality, there is very little research specifically on combinations.

Any combination should be assessed by three criteria: is there a biochemical logic, are there human data, and does the risk of side effects not increase. If the answer to the second point is «no», you should at least be confident about the third.

One more practical consideration: when you combine several new supplements at once, it is impossible to understand exactly what produced the effect or caused discomfort. That is why the editorial team advises adding components one at a time.

Below we will look at the most common combinations found on the market and explain how well-founded they are.

Citrulline, arginine, and aspartate

Ornithine, citrulline, and arginine are three links of the same urea cycle, so they are often combined into «NO complexes». There is a biochemical logic here, but it is worth understanding: for raising the plasma level of arginine, citrulline is the most effective, and ornithine has a secondary role in such a complex.

The combination of arginine with ornithine was studied in the 1980s–1990s in the context of growth hormone and strength (Elam et al., 1989). The results were ambiguous, and tolerable oral doses did not produce a convincing hormonal effect (Chromiak, Antonio, 2002).

The combination with aspartate (L-ornithine-L-aspartate) is a pharmaceutical form for patients with hyperammonemia. Aspartate also participates in the urea cycle, and their combination has an evidence base specifically in hepatology (Kircheis et al., 1997), not in sport.

Practical conclusion: ornithine can be combined with citrulline, but one should not place great expectations on such a combination for «pump» or strength. The main contribution in this case is made by citrulline.

Creatine, protein, and vitamin B6

Creatine is one of the most researched ergogenic supplements (Kerksick et al., 2018). There are no known adverse interactions between creatine and ornithine, and they can be taken on the same day. However, no synergy between them has been proven either: they act through different mechanisms.

Protein and essential amino acids (EAAs), in particular leucine, drive muscle protein synthesis. Ornithine does not perform these functions, so the logical approach is one in which the base remains sufficient protein intake, and ornithine is an optional addition.

Vitamin B6 (pyridoxine) is a cofactor of the enzyme ornithine aminotransferase, through which ornithine is converted into glutamate semialdehyde and further into proline. That is why B6 is sometimes included in formulas with ornithine. With a balanced diet, B6 deficiency is rare, and additional doses are usually not needed.

With magnesium, zinc, and vitamin B6, ornithine is often combined in «sleep and recovery» products. The data for such a combination are limited, but from a safety standpoint it raises no particular concerns at standard doses.

What to be careful with

Pre-workout complexes with ornithine often contain caffeine, synephrine, yohimbine, and other stimulants. The risks of such products are determined primarily by the stimulants: a racing heartbeat, elevated pressure, anxiety, insomnia. If you want to take ornithine to improve sleep, taking a complex with caffeine in the evening contradicts this goal.

You should not combine several «growth hormone releasers» (arginine, lysine, ornithine, GABA) in large doses in the hope of getting a cumulative effect. The result is most often not a hormonal surge but gastrointestinal discomfort due to the cumulative osmotic load.

Combination with prescription drugs deserves separate mention. People taking medication, especially with diseases of the liver and kidneys, need to clear any supplement with a doctor.

Ornithine should also not be a «cover» for hepatotoxic substances. The notion that it protects the liver during the intake of oral anabolic steroids has no evidence.

• Do not take stimulant complexes in the evening.
• Do not «stack» several amino acid releasers.
• Do not use ornithine as protection against toxic drugs.

A practical approach to combining

Start with the basics: sufficient calories, protein, sleep, and a training plan. If you already take creatine and, as needed, caffeine, those are the supplements with the best evidence base.

If you want to try ornithine, add it separately, without other new components, and assess the effect over several weeks. Only after that can you add other supplements.

Choose products with a transparent composition, where the dose of each component is listed separately. Avoid «proprietary blends» where it is impossible to understand how much ornithine you are getting.

And remember that ornithine may already be in your pre-workout or amino acid complex, so before adding a separate product, check the composition of what you already have.

Editorial conclusions

There is not much serious research on combinations with L-ornithine, so most combinations should be assessed from the standpoint of logic and safety.

Combinations with citrulline, creatine, or protein are acceptable, but synergy has not been proven. Combinations with several growth hormone «releasers» and with stimulants require caution.

The best strategy is to add supplements one at a time and honestly assess the result.

Related materials: «Leucine: what it is and how it works», «How to take L-ornithine: dosing, timing, duration», and «Myths about L-ornithine».

References

1. Elam RP, Hardin DH, Sutton RA, Hagen L. Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males. J Sports Med Phys Fitness. 1989;29(1):52–56.
2. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition. 2002;18(7–8):657–661.
3. Kircheis G, Nilius R, Held C, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology. 1997;25(6):1351–1360.
4. Kerksick CM, Wilborn CD, Roberts MD, et al. ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr. 2018;15(1):38.
5. Maughan RJ, Burke LM, Dvorak J, et al. IOC consensus statement: dietary supplements and the high-performance athlete. Br J Sports Med. 2018;52(7):439–455.
6. Sugino T, Shirai T, Kajimoto Y, Kajimoto O. L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. 2008;28(11):738–743.