Betalains

Health Benefits of Betalains

Betalains consistently demonstrate health-promoting properties in both clinical trials and mechanistic studies, making a strong case for including betalain-rich foods (like beets, chard and red dragonfruit) in our diets regularly. Among the best-studied benefits of betalains are antioxidant, anti-inflammatory, anticancer, antidiabetic and cardioprotective properties.

Antioxidant Benefits of Betalains

Betalains demonstrate a variety of health-promoting biological activities, most notably as powerful antioxidants. Betalains scavenge free radicals (a.k.a. reactive oxygen species) and can inhibit lipid peroxidation and LDL cholesterol oxidation, in addition to inducing the endogenous antioxidant system through its effect on signalling pathways that mediate the transcription of antioxidant genes.  For instance, betanin dose dependently increases the activity of the transcription factor Nrf2 which in turn actives the antioxidant response element (ARE) responsible for the transcription of several antioxidant enzymes (including phase II detoxifying enzymes).  Betanins are also thought to be involved in mitogen-activated protein kinase (MAPK) activation.  This results in the phosphorylation and stabilization of Nrf2, thereby enhancing its nuclear translocation. 

Betalains Are Anti-Inflammatory

Beets exhibit anti-inflammatory effects, mediated through their betalain content.  The anti-inflammatory effects of betalains and beetroot extract appear to be mediated by interfering with pro-inflammatory signalling cascades.  The most important of these is the NF-κB signalling cascade as it is responsible for activating and transcribing gene targets that up-regulate the inflammatory response (such as chemokines, cytokines, apoptotic and phagocytic cells).  Betalains were also reported to suppress COX-2 expression, a pro-inflammatory enzyme responsible for prostaglandin biosynthesis, to effectively repress intercellular cell adhesion molecule-1 (ICAM-1), to inhibit pro-inflammatory LOX and COX enzymes, and to reduce the levels of pro-inflammatory cytokines such as IL-6, IL-8, IL-1b and TNF-α in addition to reducing the levels of reactive oxygen and nitrogen species.  That’s a lot of benefits!

In fact, a 2005 in vitro study demonstrated that betanin inhibited COX-2 enzyme activity by 97%, which is comparable or greater than what is seen with many NSAIDs including Ibuprofen, Vioxx and Celebrex!

For example, a 2010 study evaluated the influence of betalain-rich extract in patients with osteoarthritis.  Subjects received beetroot-derived betalain-rich capsules (providing 35, 70 or 100 mg betalains per day) for 10 days.  Those receiving the intervention reported a significant reduction in pain which coincided with a reduction in pro-inflammatory cytokines.  Specifically, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) decreased from baseline by 8.3%–35% and 22%–28.3%, respectively.  The activity of pro-inflammatory chemokines, regulated oncogene-alpha (GRO-alpha) and regulated upon activation normal T cell growth (RANTES) were also markedly inhibited by the beetroot treatment.

Anticancer Properties of Betalains

Betalains have anti-cancer properties, inhibiting growth and inducing apoptosis of a variety of malignant cell types in addition to preventing DNA damage. In vitro and in vivo studies have shown promising affects in several cancer types including bladder, breast, colorectal, esophageal, leukemia, liver, lung, pancreatic, prostate, renal, and skin cancers.  For example, a 2015 study found that betanin-enriched beetroot extract induced apoptosis in breast cancer cells.  The betanin and isobetanin enriched concentrate produced from red beetroots inhibited proliferation of cancer cells and induced their death but had limited effects towards normal cells.  Cell proliferation occurred through inhibition of the cell cycle progression, by decreasing the G1 cell number, promoting the increase of S phase and down regulating cyclin A2 and cyclin B1 levels in breast cancer cells.  Expression of apoptotic-related proteins (FAS, TRAILR4, Bad and p53) was significantly induced and the mitochondrial membrane potential was altered suggesting that both intrinsic and extrinsic pathways were involved. 

Interestingly, a 2013 study demonstrated synergistic cytotoxicity of red beetroot extract with doxorubicin (anti-cancer drug) against human pancreatic, prostate and breast cancer cell lines.  Different concentrations of beet extract (B) and doxorubicin (D) in various combinations (B:D ratio = 1:0, 1:1, 5:1, 1:5 and 0:1) were tested for cytotoxic effects against the three cancer cells.  After 72 hours of incubation, the results indicated an overall positive reduction in the required concentration of doxorubicin when combined with beet extract, suggesting a potential combination treatment for cancer.  Enhancing the therapeutic efficacy of the chemotherapy drug could help reduce toxic side-effects in patients as a consequence of reducing overall drug dose. 

Betalains and Insulin Resistance

Across numerous studies, betalains have been shown to lower serum glucose levels, decrease the postprandial glucose response and insulin secretion (even in people drinking 300 grams of glucose together with 250mL of beetroot juice) and even protect against complications of diabetes, such as kidney injury.

For example, a 2014 randomized, single-blind, placebo-controlled, cross-over study evaluated the effects of beetroot juice on insulin response.  Participants consumed 225 mL beetroot juice, a control beverage matched for macronutrient content, or a glucose beverage.  Those consuming beetroot juice had a significant lowering of the postprandial insulin response in the first 60 minutes and a significantly lower glucose response in the first 30 minutes. 

Multiple mechanisms are suggested to be responsible for the observed regulation of insulin and glucose homeostasis.  Betanin contributes to AMPK activation which contributes to increases in insulin secretion.  Betalains also help reduce carbohydrate digestion and intestinal glucose absorption, all of which result in a suppression of the postprandial glucose response. 

Betalains and Cardiovascular Disease Risk

Betalains improve lipid profiles, including reducing total cholesterol, triglycerides and LDL cholesterol while increasing HDL cholesterol.

In a 2019 clinical trial of obese people, consuming 28 grams of freeze-dried red beet leaves resulted in improved serum lipids as well as weight loss. In another 2019 randomized controlled trial, non-smoking adults with coronary heart disease were given a betalain-rich supplement of red beetroot (50 mg per day) for 2 weeks.  At the end of the study subjects had decreased levels of homocysteine, glucose, total cholesterol, triglycerides and LDL-cholesterol.  In addition, significant reductions in systolic and diastolic blood pressure were observed.  The authors suggested that the observed antihypertensive effect may have been mediated by the reductions observed in plasma homocysteine levels.

Other Benefits of Betalains

Betalains also have antiviral, antifungal, antiprotozoal, and antibacterial activity, including inhibiting the growth of a very wide range of pathogens. Furthermore, betalains have hepatoprotective effects and improve detoxification via increased phase II detoxifying enzymes. Animal models demonstrate neuroprotective properties of betalains as well, with potential benefit for neurodegenerative diseases including Alzheimer’s and Parkinson’s disease.