Bitter Orange: An Alternative to DMAA

On April 27, 2012, the U.S. Food and Drug Administration issued a warning letter to 10 fitness supplement companies selling weight loss and sports nutrition products containing the controversial ingredient, DMAA. The FDA further warned that DMAA was not a botanical ingredient since it is synthetically produced and therefore ineligible to be used as an active ingredient in a dietary supplement. Citing several harmful effects of DMAA, the FDA ordered said companies to immediately take remedial steps to address these concerns.¹

What are the Side Effects of DMAA?
DMAA, commonly sold as 1,3- dimethylamylamine, methylhexanamine, or geranium extract, is a synthetic substance popularly used in bodybuilding and weight-loss products. DMAA is said to have potentially fatal side effects on cardiovascular health leading to events such as shortness of breath, tightening of chest, heart attacks and elevated blood pressure. After 42 public complaints, the FDA issued a warning linking DMAA to serious health effects on the nervous system and psychiatric disorders as well as death.²
The controversy: Is DMAA a Drug?
The controversy over DMAA doesn’t end here. Is DMAA a botanical substance or synthetic? Since DMAA is manufactured in laboratories, many experts believe it is not a botanical substance, but an amphetamine-like substance which should be treated as a drug. It should undergo rigorous testing standards and be approved by the FDA as a drug. In light of these heated controversies, supplement business owners are busy looking for safer substitutes for DMAA in their weight-loss and sport nutrition formulations. One option is to substitute DMAA with the herbal substance, bitter orange, as their benefits are similar.
Health Benefits of Bitter Orange
Bitter orange is prepared from the bitter orange fruit, botanically known as Citrus aurantium. For centuries the Chinese and the tribes of the Amazon rainforests have used it to treat indigestion, nausea and constipation. Bitter orange supplements are believed to treat heartburn, appetite loss, nasal congestion, weight loss and fungal infections. The two bioactive ingredients in bitter orange are synephrine and octopamine. Both are stimulants that help to increase rate of body metabolism.³However, because its chemical structure is similar to ephedra, some people mistakenly believe that bitter orange has the same negative side effects as ephedra. Bitter orange contains the active compound p-synephrine. Does p-synephrine have the same dangerous side effects as ephedra? Let’s find out.
Is P-Synephrine Dangerous?
Hundreds of studies report the safety and efficacy of p-synephrine. An abstract from “A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects” published in the 2011 Volume of Oxidative Medicine and Cellular Longevity states:⁴
“Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.”
Another extensive study highlights the reasons for the confusion about bitter orange:⁵
“Current confusion regarding the safety and efficacy of bitter orange extract and p-synephrine is clouded by multiple issues, including the use of complex mixtures of ingredients in products that include bitter orange extract, the release of misleading information by governmental agencies, and misunderstandings regarding the isomeric forms of synephrine and their differing pharmacological properties. In addition, the projected warnings regarding cardiovascular risks are extrapolated from studies involving m-synephrine and ephedrine which are not components of bitter orange extract, and from studies involving the intravenous administration of p-synephrine at concentrations that are not attained by oral ingestion in foods or supplements.”
The study goes on to reveal a few more valid points: ⁶
“A final consideration regarding the safety of p-synephrine is the exposure of millions of people who daily consume, without ill effect, various juices and food products as marmalade from Citrus species as
Seville orange, grapefruit, mandarin and other orange-related species that contain p-synephrine.⁷

• A typical sweet orange contains about 6mg p-synephrine.⁸
• A wide variety of Citrus juices contain approximately 5mg p-synephrine per 8 ounce glass.⁹
• A U.S. Department of Agriculture study of the p-synephrine content of mandarin orange juice from 10 different groves in California found that the p-synephrine content ranged from 73 to 158 mg/L, with an overall mean of 93 mg/L.¹⁰
• Another study has shown the juice from Clementines, a variety of mandarin oranges, contained on average of 114mg p-synephrine/L while Marrs sweet oranges yielded 85 mg/L.¹¹

Therefore, consuming an 8 ounce glass of mandarin orange juice may deliver as much as 40mg
P-synephrine, similar to the amount of p-synephrine in the typical dietary supplement.”

Bitter orange: An effective substitute forDMAAin your supplement formulations.
Bitter orange is the ideal replacement for DMAA in your weight loss or sports nutrition products. Find a reliable supplement manufacturer that has a track record of contract manufacturing success. A supplement manufacturer with an award-wining history will ensure you get products that stand out in the marketplace. Look for optional manufacturing solutions such as label design, packaging options, order fulfillment and storage options that can it make it convenient for you to manufacture your product.
Resources:

1. FDA challenges marketing of DMAA products for lack of safety evidence, April 27, 2012. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm302133.htm
2. Ibid.
3. Bitter Orange, Drugs.com. drugs.com/npp/bitter-orange.html
4. A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects, Oxidative Medicine and Cellular Longevity Volume 2011 (2011), Article ID 482973, 9 pages, doi:10.1155/2011/482973. hindawi.com/journals/oximed/2011/482973/abs/
5. The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p‐Synephrine, PHYTOTHERAPY RESEARCH, Phytother. Res. (2011), Published online in Wiley Online Library(wileyonlinelibrary.com) DOI: 10.1002/ptr.3490. nutratechinc.com/advz/UploadedFiles/Phyto%20Research%200411.pdf
6. Ibid
7. Pellati et al.,2002, 2004, 2005; Blumenthal, 2004; Avula et al., 2005; Mattoli et al., 2005; Dragull et al., 2008; Arbo et al., 2008; Roman et al., 2008.
8. Mattoli et al., 2005.
9. Blumenthal, 2004; Pellati et al., 2002, 2004, 2005.
10. Dragull et al., 2008.
11. Uckoo et al.,2010.