In a 1992 patent by Emanuel Revici, MD, heptanoic acid is referenced as a viable treatment for AIDS (1). Accordingly, 3 odd-carbon fatty acids are discussed, pentanoic (C-5), heptanoic (C-7), and nonanoic (C-9). According to this patent, Revici claims that these 3-odd carbon fatty acids (especially heptanoic) “exhibit not only anti-HIV virus effects, but also affect the parasitated or infected lymphocytes, killing them”. Additionally, claims within this patent refer to the oral administration of heptanoic acid in a 50% immersion (with safflower oil as the carrier) 2-4x daily to a group of 40 AIDS patients. The claims relating to the resulting effects are impressive, with significant improvements in symptoms, body weight, the T4/T8 ratio, among other parameters.
Updating the Understanding of Heptanoic Acid 30 Years Later
It is often stated by those “in the know”, that Emanuel Revici was a physician and scientist who was decades ahead of his time. With the emerging understanding of heptanoic acid as proposed for a variety of conditions, Revici’s genius has once again shone through into the future.
In June of 2020, the FDA approved the use of a drug, Dojolvi, for the treatment of long-chain fatty acid oxidation disorders. Dojolvi is composed of the triglyceride of heptanoic acid, referred to as ‘Triheptanoin’. An additional body of literature identifies Triheptanoin as a potential treatment for a variety of different conditions, including:
- Epilepsy (2)
- ALS (3)
- GLUT1 deficiency (4)
- Pyruvate carboxylase deficiency (5)
- Alzheimer’s disease (6)
- Huntington’s disease (7)
Heptanoic Acid & Anaplerosis
Anaplerosis refers to the replenishment of what is missing. It is now understood that Heptanoic Acid acts in large part by rapidly replenishing energy substrates to the Kreb’s cycle. Uniquely, it does this without the need for an active transport molecule to the mitochondria, such as the carnitine shuttle (8). The resultant effect of intracellular heptanoic acid is the generation of 2 molecules of Acetyl coenzyme A, and 1 molecule of propionyl coenzyme A. While increased acetyl coenzyme A substrates are of obvious potential benefit, the formation of propionyl coenzyme A leads to the formation of succinyl coenzyme A. This succinate molecule acts both as a Kreb’s cycle intermediate, as well as in complex 2 of the mitochondrial respiratory chain (8). In the liver, the ß-oxidation metabolite of propionyl-derived heptanoic acid is converted into gluconeogenesis substrates and C-5 ketones. Both heptanoate and C-5 ketones replenish missing energy molecules to mitochondria (9).
It is now contested that AIDS (acquired immune deficiency syndrome) can be better understood as AEDS (acquired energy deficiency syndrome), involving a variety of mechanisms related to insufficient mitochondrial function of various cell types, including T-cell lymphocytes (N.T. Banks, 2016; H. Kremer; 2008). Fast forwarding to 2023, Revici’s claimed benefit of heptanoic acid for AIDS can be seen within the larger context of anaplerosis, and the replenishment of the pool of mitochondrial energy substrates.
Moreover, in light of emerging system’s biology research that showcases how varying degrees of mitochondrial dysfunction are at the core of the chronic disease puzzle (R.K. Naviaux, 2019), the potential uses of heptanoic acid, and other odd carbon fatty acids (such as pentanoic and nonanoic acids) is appealing across a wide range of diseases, which involve mitochondrial energy disturbances.
Revici’s System of Medicine: Anabolic & Catabolic
Emanuel Revici, MD was a physician who practiced medicine for more than 70 years. He was referred to by many of his contemporaries as “The Einstein of Chemistry”. He treated tens of thousands of patients and is most remembered for a chain of scientific discoveries, as well as the creation of an entire arsenal of therapeutic lipid inventions and treatments, for a variety of medical conditions.
Revici’s body of work stems from his discovery and elucidation of a Lipidic Defense system operative within organisms. This system consists of intertwined, dynamic forces that he referred to as “Anabolic” and “Catabolic”. Anabolic forces are comprised of constructive and “negentropic” processes. Catabolic forces are comprised of consumptive, as well as destructive and “entropic” processes. Anabolic lipids are those with positively charged polar groups, namely cholesterol, sterols, cortisol, estrogen and glycerol. Catabolic lipids are mainly comprised of various fatty acids, and ketones, especially polyunsaturated fatty acids containing 2 or more consecutive double bonds (such as arachidonic acid, leukotrienes, linoleic acid). While the anabolic and catabolic forces are operative all of the time in every organism, they play a vital role in pathology.
Revici found that the interplay of anabolic and catabolic lipids interact on all levels of hierarchical organization, from sub-cellular, to cellular, to tissue, to organ and organism. A key Revici concept is that in pathology, either the anabolic or the catabolic force will tend to predominate. Inflammatory diseases tend to be more catabolic in nature. There is more oxygen run amok, and the proclivity towards the generation of ROS (reactive oxygen species), lipid peroxides and inflammatory eicosanoid signaling. Anabolic diseases are seen in conditions such as diabetes, cardiovascular disease, the initial stages of cancer, and conditions involving fibrosis and sclerosis.
The effect of heptanoic acid has the qualities of a catabolic lipid. The increased functionality of mitochondria produced by heptanoic acid can also be thought of as catabolic, because the oxidation of energy substrates within mitochondria generates more reactive oxygen species and increases the utilization of oxygen. Because heptanoic acid leads to increased succinyl coenzyme A, this has the net effect of increasing fatty acid utilization in mitochondria. Also, the increased generation of ketones in the liver derived from heptanoic acid can also be thought of as catabolic.
Revici found that AIDS is predominantly an anabolic condition. Think of anabolic in this context as defined by mitochondrial dysfunction, a core characteristic of AIDS pathophysiology. The other conditions for which heptanoic acid have recently been considered can also be thought of as anabolic as well. This may be useful because Revici developed an entire arsenal of “anti-anabolic” treatments, such as bivalent negative selenium, hydropersulfide and other sulfur preparations, sodium and magnesium thiosulfate, just to name a few. In fact, Revici had an entirely different way of interpreting the periodic table of the elements, with respect to the classification of the anabolic and catabolic characters of most elements.
Emerging System’s Biology Finds Striking Parallels with Revici
Dr. Robert Naviaux’s research into the cell danger response (CDR) has many distinct parallels with Revici’s findings. For example, Naviaux’s 2019 paper published in the journal Mitochondrion elucidates upon the cell danger response as the body’s healing cycle itself (10). In this healing cycle, the first phase (CDR-1) is very similar to Revici’s classification of the Catabolic force. Whereas CDR-2 is very similar to Revici’s defined Anabolic force. Additionally, Naviaux’s research using metabolomics and system’s biology finds that lipid dysregulation is of high significance in many disease states. No doubt, this research is of great interest for those seeking to advance medicine into personalized modes of treatment, beyond the current practice of ‘production line medicine’ and linear-model centricity.
Among Revici’s many contributions, his ability to utilize his extraordinary depth of chemistry for the development of new therapeutics is arguably still decades ahead of its time. In this regard, a deep dive into Revici’s therapeutic inventions will likely fill missing gaps for the treatment of chronic disease in the modern era. Heptanoic Acid is but one example.