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In a recent study published in the journal Nutrients, researchers in Australia examine the health benefits associated with capsaicin, with a particular focus on how this compound impacts cognition and cardiovascular health.

Study: Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing. Image Credit: Kiattipong / Shutterstock.com

What is capsaicin?

Capsaicinoids, which are the major pungent chemical found in Capsicum-genus plants like chilies, are phenolic compounds that share a vanilloid ring. Capsaicinoids consist of capsaicin, nordihydrocapsaicin, erythromycin nursing mothers homocapsaicin, dihydrocapsaicin, and homodihydrocapsaicin, of which capsaicin has the highest prevalence. Capsaicin is associated with numerous health benefits including anti-inflammatory, anti-carcinogenic, anti-obesity agent, and antioxidant properties.

Capsaicin and cardiometabolic disease

Obesity elevates blood triglycerides, low-density lipoprotein (LDL), and free fatty acids. This contributes to vascular remodeling, nitric oxide synthase (NOS) dysregulation, and atherosclerosis, the latter of which is a major reason for cerebrovascular and cardiovascular disease.

Capsaicin enhances thermogenesis, fat oxidation, and energy expenditure, all of which contribute to reduced adiposity. This is accomplished by transient receptor potential vanilloid channel 1 (TRPV1) activation and the subsequent lowering of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which are elevated with higher adiposity.

Previously, TRPV1 activation with capsaicin has been shown to reverse defective macrophage autophagy produced by oxidized low-density lipoprotein, as well as activate AMP-activated protein kinase (AMPK) signaling activation, reduce foam cell production, and limit the formation of atherosclerotic plaques.

Aging, cognition, and capsaicin

One of the primary symptoms of dementia is impaired cognition, which can result in functional impairment and diminished quality of life in an aging population. Increased oxidative stress, endothelial dysfunction, and persistent low-grade systemic inflammation are related to aging and can subsequently lead to impaired cerebrovascular function and cognitive impairment.

Through TRPV1 activation, capsaicin has been shown to improve cognition in vivo. To this end, TRPV1 activation induced by capsaicin leads to reduced adiposity, oxidative stress, and chronic low-grade systemic inflammation, all of which are associated with both cerebrovascular function and cognition.

Capsaicin improves cognition in mice and humans

Tau proteins, which are involved in microtubule formation, are enriched in the central nervous system (CNS). Abnormal tau proteins can elevate phosphorylation and reduce microtubule binding, subsequently resulting in the formation of amyloid oligomers and aggregated deposits. These amyloid deposits can impair brain function by lowering intra- and inter-neuronal signaling, thus causing cognitive decline.

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The intraperitoneal (IP) injection of capsaicin to C57BL/6 mice for two weeks repaired Aβ-induced memory impairments by enhancing hippocampal synaptic function. This may have been due to the increased production of postsynaptic density protein 95 (PSD95), which is a neuroprotective protein that is frequently diminished in Alzheimer's disease.

Cholinesterase enzymatically degrades acetylcholine, which is a potent vasodilatory cholinergic neurotransmitter that reduces with aging. Cholinesterase activity is elevated in Alzheimer's disease, which leads to further reduced levels of acetylcholine.

Cholinesterase inhibitors are currently the first-line therapy for AD. According to research, 13 days of consuming capsaicin-containing chili oleoresin in addition to the anticholinergic scopolamine reduced acetylcholinesterase (AChE) by 50%.

Using a food frequency questionnaire, one study investigated the consumption of chili peppers by 338 community-dwelling individuals in Chongqing, China. To this end, a diet high in capsaicin was associated with considerably higher mini-mental state examination (MMSE) scores.

In the aforementioned study, those who ate chilies on a daily basis were younger as compared to those who self-reported weekly intake. This was ascribed to the social assumption that older individuals prefer blander meals.

Taken together, these findings suggest that capsaicin may affect human brain health. However, additional research is needed to determine the consequences of chronic chili consumption on cognition.

The effects of capsaicin on cerebrovascular function

Previous in vitro investigations have revealed that a small dose of capsaicin led to the vasodilation of pial arteries, whereas a higher dose caused vasoconstriction.

In another in vivo study, using a Doppler flowmeter positioned across the middle meningeal artery of rats, researchers assessed the effect of a dural administration of capsaicin on meningeal blood flow. Meningeal afferents released more calcitonin gene-related peptide (CGRP) in response to high and low topical capsaicin treatment on the dura mater.

Notably, the release of CGRP was shown to be greater in obese rats in comparison to control rats. This may be related to decreased sensitivity of CGRP receptors to CGRP.

Capsimax

Capsimax is an easily accessible supplement consisting of 2% capsaicinoids derived from 15% to 25% Capsicum extract, 45% to 55% sucrose, and 30% to 35% cellulose gum coatings. This supplement prolongs the release of capsaicin into the small intestine, which eliminates its pungency and other problems related to direct chili or capsaicin administration.

Capsimax has been shown to increase thermogenesis and reduce lipogenesis, as demonstrated by lower fatty-acid binding protein and peroxisome proliferator-activated receptor gamma levels.

Similarly, oxidative inflammation and stress were reduced in male Wistar rats administered Capsimax every day for eight weeks in conjunction with exercise, a low-fat, a high-fat diet, or a high-sucrose diet. Lowered nuclear factor erythroid-related factor 2 (NFE2L2) and nuclear factor-κB (NF-κB) were determined to be responsible for this effect.

Conclusions

Capsimax is a new, safe, and tolerated capsaicin supplement that reduces the likelihood of gastrointestinal distress and other unwanted side effects of capsaicin consumption. Considering the paucity of available preventive therapies for cognitive loss, capsaicin may represent a natural treatment for cognitive decline. Nevertheless, future studies are needed to determine if the ability of capsaicin to reduce cognitive could lead to a reduced risk of diseases like dementia and AD.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.