With the rise of autodidactic biohacking and the public accessibility of science, dietary supplements and nootropics have come under more (justifiable) scrutiny; not the usual faux scrutiny by charlatans who worship doctors and pharmaceuticals, but instead reasonable and empirically-based concern. Meanwhile, marketing of overpriced health products and blends composed of various otherwise inexpensive compounds has increased, along with grandiose and slanted claims. 

For a minimalist, or anyone without the funds to risk on peddled marketing ploys, I think it’s important to adopt the same conservative approach to your lifestyle as to your diet and supplements. I consider zero supplements as ideal, and many powerful compounds can be obtained via foods, but obviously everyone’s situation is unique and experimentation can be useful. If someone is going to take supplements and nootropics, prioritizing the cheapest, most ubiquitous and ancient compounds, and exploiting their benefits, has a special appeal.

The rapid and recent rise of cinnamon research publications.

Cassia cinnamon is the cheaper and more common variety, and contains the compound coumarin, which is liver-toxic and carcinogenic, at extremely high levels compared to Ceylon cinnamon, the more expensive and less common variety. More recently, Taiwan’s cinnamomum osmophloeum has been identified as a cheaper low-coumarin cinnamon source (Yeh, et al., 2014), but it’s not yet commercially available. There is enough coumarin in cassia cinnamon to cause liver toxicity in susceptible people, at relatively modest dietary intake of cinnamon.

Cassia cinnamon powder contains up to 63 times more coumarin than Ceylon cinnamon powder, and cassia sticks up to 18 times more coumarin than Ceylon sticks (Woehrlin, et al., 2010). It’s important to know the properties of what you’re ingesting, since industrial profit-efficiency takes precedence over health.

The cinnamaldehyde in cinnamon is responsible for its aroma and flavor, but it and its metabolites also possess anti-cancer, anti-bacterial, anti-inflammatory, pro-metabolic, brain-protective properties. For example, cinnamaldehyde prevents cells from destroying themselves during stress, preserves their mitochondrial capacities, and blocks the generation of inflammatory cytokines like tumor necrosis factor-alpha and interleukin-1 beta by inhibiting their receptor signaling at Toll-like receptor 4 and the NF-kappa B complex (Youn, et al., 2008; Hajinejad, et al., 2020).

Brain and Cognition

Much of cinnamon’s brain benefits are traced to its metabolite, sodium benzoate (which is also added to certain soft drinks), which upregulates neuroplasticity-related molecules, and stimulates the excitatory NMDA and AMPA receptors to take up more calcium (which can be good or bad, contextually).

In mice found to have poor learning ability, one month of cinnamon intake increased their spatial memory consolidation via sodium benzoate’s induction of protein kinase A, which in turn increases the CREB transcription factor in the hippocampus. When the cinnamon-treated mice’s neurons were observed microscopically, their hippocampal dendrites (branched ends used for communication) were larger, more mature, and more numerous (Modi, et al., 2016).

The progression of Parkinson’s disease involves the destruction of dopaminergic neurons in the substantia nigra. Astrocytes (regulatory brain cells) produce proteins like Parkin and DJ-1 that protect the brain from this destruction, but the inflammation already contributing to the Parkinson’s hinders those protective proteins. The cytokine interleukin-1 beta directly inhibits Parkins and DJ-1, and tumor necrosis factor-alpha leads to nitric oxide release, which negates them further. However, cinnamon powder in the diet of Parkinson’s mice restores their astrocytic Parkin and DJ-1 and leads to a normalization of their neurotransmitters and improvement of their motor function (Khasnavis & Pahan, 2014).

I have written previously about endotoxin, or lipopolysaccharide (see: “Endotoxin’s Role in Degeneration and Disease; Protective Factors to Mitigate it”). Cinnamon powder is yet another simple antidote to endotoxin exposure. Endotoxin leads to reactive oxygen species (ROS) production in microglial cells (immune defense neurons), one mechanism that leads to neurodegeneration such as in Alzheimer’s. Cinnamon’s sodium benzoate is able to prevent this ROS production, increase brain glutathione, reduce homocysteine and amyloid beta-plaques (elevated homocysteine is seen in dementia and heart disease, and amyloid beta-plaques are an epiphenomena of neurodegeneration), and suppress the programmed neuron death that occurs due to endotoxin (Modi, et al., 2015).

In mice, cinnamon extract added to drinking water “almost completely” mitigated the memory impairment and neuron loss after traumatic brain injury, when consumed one week before and two weeks after the injury. The mice who did not drink cinnamon extract demonstrated the typical severe impaired memory and neuron loss after their traumatic brain injury (Qubty, et al., 2021)

Cancer

Two of cinnamaldehyde’s metabolites, 2-hydroxycinnaldehyde (HCA) and 2-benzoyloxycinnamaldehyde (BCA) have demonstrated anti-cancer abilities and are being primed for further research, since they are poorly bioavailable in their naturally occurring form and require pharmacological modification if they are to become realistic adjuvant cancer treatments (Iqbal, et al., 2021). A liquid extract of Ceylon cinnamon tree bark destroys cancer cells and halts their division, attributed to properties of cinnamaldehyde, 4-hydroxycinnamic acid, and eugenol (Varadarajan, et al., 2020).

In vitro, cinnamaldehyde and eugenol effectively destroy colorectal cancer cells after 72 hours of treatment, while sparing the normal mucosal epithelial cells also treated (Petrocelli, et al., 2021).

Gut Health

The cinnamaldehyde and eugenol in cinnamon, delivered via diluted essential oil, is a powerful intestinal protectant and medicine. Cinnamon oil cripples the metabolism of fungi (Lai, et al., 2021) and kills larvae (e.g. of mosquitos and silverfish) making it a potentially useful industrial pesticide and insecticide, but this applicability extends to internal use for health.

Cinnamon oil, even from cassia cinnamon, is a potent antimicrobial against the top 6 strains of E. coli, excluding the top strain, O157. At the low concentration of 10 drops per liter of water, it killed all 6 strains within 24 hours (Sheng & Zhu, et al., 2014).

By shifting amino acid regulation in intestinal mucosa in favor of cysteine, glutamate, and glycine, cinnamon upregulates intestinal glutathione production, glutathione being one of the major endogenous antioxidants, protecting against inflammatory insults like endotoxin and preserving the barrier function of the intestine (lack of the barrier function being what people call “leaky gut”.) In piglets, 50mg/kg of cinnamon oil protected them against endotoxin poisoning by reducing mucosal damage and diarrhea, and accelerating mucosal repair (Wang, et al., 2015). The same dose of cinnamon oil included in piglet diets was so effective as an antibiotic, antiviral, and metabolic enhancer, that researchers concluded it is an effective alternative to traditional antibiotics (Yi, et al., 2018). Pig models in nutrition related to gut barrier function have been assessed as practically comparable to humans (Roura, et al., 2016).

Metabolism

Cinnamon improves glucose metabolism by raising insulin-receptor beta insulin receptor substrate 1 (IRS-1), a rate-limiting protein for insulin receptor function. When blood glucose is circulating, insulin receptors attach IRS-1 to the enzyme phosphoinositide 3-kinase to form a complex necessary to take glucose into the cell. In animals, lower cinnamon doses barely work, but at doses high enough to phosphorylate IRS-1, muscle cells absorb glucose more efficiently which translates to better performance, energy, and growth (Qin, et al., 2003). 

In humans, even “lower” doses are effective: as little as ½ a teaspoon (1g) of cinnamon significantly improved glucose metabolism and blood markers in diabetic and non-diabetic patients (Khan, et al., 2003). It is important to note that regularly consuming that amount of cassia cinnamon is likely dangerous and Ceylon cinnamon is always preferred.

Migraines

Inflammatory molecules contribute to migraine attacks in a subset of migraine patients. Interleukin-6, calcitonin-gene-related-peptide (CGRP), and nitric oxide mediate neuroinflammatory pain, and migraineurs are more sensitive to, and produce more of, these mediators. In fifty migraine patients given either placebo or 600mg cinnamon, the cinnamon group experienced a significant reduction in the inflammatory interleukin-6 cytokine and nitric oxide, and a reduction in migraine occurrence, severity, and length, compared to placebo (Zareie, et al., 2020).

Skin

Cinnamon (particularly its cinnamaldehyde) reduces skin aging by amplifying insulin-like growth factor 1’s enhancement of collagen in skin cells (Takasao, et al., 2012). The progressive loss of skin collagen production is the principal mechanism behind skin’s visual deterioration in aging.

Works Cited

Angelopoulou, Efthalia, et al. “Neuroprotective Potential of Cinnamon and Its Metabolites in Parkinson’s Disease: Mechanistic Insights, Limitations, and Novel Therapeutic Opportunities.” Journal of Biochemical and Molecular Toxicology, 2021, doi:10.1002/jbt.22711.

Hajinejad, Mehrdad, et al. “Natural Cinnamaldehyde and Its Derivatives Ameliorate Neuroinflammatory Pathways in Neurodegenerative Diseases.” BioMed Research International, vol. 2020, 2020, pp. 1–9., doi:10.1155/2020/1034325.

Hariri, Mitra, and Reza Ghiasvand. “Cinnamon and Chronic Diseases.” Advances in Experimental Medicine and Biology Drug Discovery from Mother Nature, 2016, pp. 1–24., doi:10.1007/978-3-319-41342-6_1.

Hou, Yongqing. “Beneficial Roles of Dietary Oleum Cinnamomi in Alleviating Intestinal Injury.” Frontiers in Bioscience, vol. 20, no. 5, 2015, pp. 814–828., doi:10.2741/4339.

Iqbal, Haroon, et al. “Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2-Benzoyloxycinnamaldehyde: Where Do We Stand?” Combinatorial Chemistry & High Throughput Screening, vol. 24, 2021, doi:10.2174/1386207324666210216094428.

Kawatra, Pallavi, and Rathai Rajagopalan. “Cinnamon: Mystic Powers of a Minute Ingredient.” Pharmacognosy Research, vol. 7, no. 5, 2015, p. 1., doi:10.4103/0974-8490.157990.

Khan, A., et al. “Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes.” Diabetes Care, vol. 26, no. 12, 2003, pp. 3215–3218., doi:10.2337/diacare.26.12.3215.

Khasnavis, Saurabh, and Kalipada Pahan. “Cinnamon Treatment Upregulates Neuroprotective Proteins Parkin and DJ-1 and Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease.” Journal of Neuroimmune Pharmacology, vol. 9, no. 4, 2014, pp. 569–581., doi:10.1007/s11481-014-9552-2.

Kim, Jun-Ran, et al. “Insecticidal Activity of Cinnamon Essential Oils, Constituents, and (E)- Cinnamaldehyde Analogues against Metcalfa Pruinosa Say (Hemiptera: Flatidae) Nymphs and Adults.” Korean Journal of Applied Entomology, 2015, pp. 375–382., doi:10.5656/ksae.2015.10.0.056.

Lai, Tongfei, et al. “Cinnamon Oil Inhibits Penicillium Expansum Growth by Disturbing the Carbohydrate Metabolic Process.” Journal of Fungi, vol. 7, no. 2, 2021, p. 123., doi:10.3390/jof7020123.

Modi, Khushbu K., et al. “Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement.” Journal of Neuroimmune Pharmacology, vol. 11, no. 4, 2016, pp. 693–707., doi:10.1007/s11481-016-9693-6.

Modi, Khushbu K., et al. “Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer’s Disease.” Plos One, vol. 10, no. 6, 2015, doi:10.1371/journal.pone.0130398.

Petrocelli, Giovannamaria, et al. “Molecules Present in Plant Essential Oils for Prevention and Treatment of Colorectal Cancer (CRC).” Molecules, vol. 26, no. 4, 2021, p. 885., doi:10.3390/molecules26040885.

Qin, Bolin, et al. “Cinnamon Extract (Traditional Herb) Potentiates in Vivo Insulin-Regulated Glucose Utilization via Enhancing Insulin Signaling in Rats.” Diabetes Research and Clinical Practice, vol. 62, no. 3, 2003, pp. 139–148., doi:10.1016/s0168-8227(03)00173-6.

Qubty, Doaa, et al. “Orally Administered Cinnamon Extract Attenuates Cognitive and Neuronal Deficits Following Traumatic Brain Injury.” Journal of Molecular Neuroscience, vol. 71, no. 1, 2020, pp. 178–186., doi:10.1007/s12031-020-01688-4.

Roura, Eugeni, et al. “Critical Review Evaluating the Pig as a Model for Human Nutritional Physiology.” Nutrition Research Reviews, vol. 29, no. 1, 2016, pp. 60–90., doi:10.1017/s0954422416000020.

Sheng, Lina, and Mei-Jun Zhu. “Inhibitory Effect of Cinnamomum Cassia Oil on Non-O157 Shiga Toxin-Producing Escherichia Coli.” Food Control, vol. 46, 2014, pp. 374–381., doi:10.1016/j.foodcont.2014.05.050.

Takasao, Naoko, et al. “Cinnamon Extract Promotes Type I Collagen Biosynthesis via Activation of IGF-I Signaling in Human Dermal Fibroblasts.” Journal of Agricultural and Food Chemistry, vol. 60, no. 5, 2012, pp. 1193–1200., doi:10.1021/jf2043357.

Woehrlin, Friederike, et al. “Quantification of Flavoring Constituents in Cinnamon: High Variation of Coumarin in Cassia Bark from the German Retail Market and in Authentic Samples from Indonesia.” Journal of Agricultural and Food Chemistry, vol. 58, no. 19, 2010, pp. 10568–10575., doi:10.1021/jf102112p.

Yeh, Ting-Feng, et al. “A Potential Low-Coumarin Cinnamon Substitute: Cinnamomum Osmophloeum Leaves.” Journal of Agricultural and Food Chemistry, vol. 62, no. 7, 2014, pp. 1706–1712., doi:10.1021/jf405312q.

Yi, Dan, et al. “Dietary Supplementation with Oleum Cinnamomi Improves Intestinal Functions in Piglets.” International Journal of Molecular Sciences, vol. 19, no. 5, 2018, p. 1284., doi:10.3390/ijms19051284.

Youn, Hyung S., et al. “Cinnamaldehyde Suppresses Toll-like Receptor 4 Activation Mediated through the Inhibition of Receptor Oligomerization.” Biochemical Pharmacology, vol. 75, no. 2, 2008, pp. 494–502., doi:10.1016/j.bcp.2007.08.033.Zareie, Azadeh, et al. “Effect of Cinnamon on Migraine Attacks and Inflammatory Markers: A Randomized Double‐Blind Placebo‐Controlled Trial.” Phytotherapy Research, vol. 34, no. 11, 2020, pp. 2945–2952., doi:10.1002/ptr.6721.

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