BEETROOT

Clinical trials frequently use beetroot as a concentrated juice in dose ranges 2 x 70mL daily, not higher. Due to its benefits to athletic performance, some researchers have proposed beetroot supplementation during oncology for preservation of muscle mass. Clinical evidence is, however, limited to a single 2015 case study in leukemia where beetroot-carrot juice significantly improved a patient outcome with standard oncology drugs. (Highlight 1)

2024 research in cardiovascular disease with daily 2x 70mL beetroot juice showed measurably improved oxidative stress, immune cell profiles, and LDL cholesterol (Highlight 2). The weakening of blood vessel integrity through systemic inflammation has been shown in pre-clinical animal trials to play a crucial role in metastasis, including in breast cancer. Poor blood vessel health is linked to high metastatic spread in these lab studies. Studies on inflammatory markers show some positive effects, particularly with more than 3-4 weeks of intake, where c-reactive protein levels decined in at least one, but not all, trials. Some effects have also been shown in reducing vascular cellular adhesion, in some trials.

There is evidence of reduced levels of platelet aggregation as an effect of beetroot juice and indications in lab study of reduced adhesion but more is needed to classify this as anti-metastatic.

In osteoarthritis clinical studies, the nitrate rich betalains in beets showed reductions in the range of one third to a half in levels of Advanced Oxidation Protein Products (AOPPs). These biomarkers of oxidative stress and inflammation have been strongly associated to breast cancer progression in a 7 year patient follow up study from 2024, and in other research similarly linked with kidney cancer. (Highlight 3). AOOP levels are proposed as a diagnostic marker in oncology.

In other disease sudies, results included improvements in microbiota, with several key bacteria including akkermansia and roseburia increasing their natural levels, driving some of the effects seen in cardivascular health.

EXAMPLES OF IMPROVED OUTCOMES

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PRE-DIAGNOSIS OR PREVENTION

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Highlighted Studies

Beetroot-carrot juice, when used in right combination and dose could enhance the therapeutic efficacy of the potent antileukmic drug chlorambucil, by reducing its toxic side-effects. A possible synergistic effect of consumption of beetroot-carrot juice with chlorambucil resulted in a substantial improvement in renal function by acting as a kidney cleanser and protects the patient from renal impairement. Furthermore, beetroot-carrot juice could be used as natural alternative treatment for CLL ...

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..the consumption of concentrated nitrate-rich beetroot juice regularly for 4 weeks had a favorable effect on the oxLDL/NOx and GSH/GSSG ratios in middle-aged and older men and women with treated hypertension. The increased GSH/GSSG ratio, in particular, tentatively supports the concept that the regular intake of vegetable-derived nitrate modulates the redox balance within the blood circulation toward a less pro-oxidative profile

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The data show a significant broad range in baseline of AOPP at day 1 in each experimental group…this range was significantly reduced in each group after 10 days of the treatment. Resulting sum data show 36.3%, 47.6% and 30.9% reduction in groups 1, 2 and 3, respectively….The results presented herein are only indicative but justify further clinical investigation on OA subjects with increased serum AOPP levels. AOPP is known as a pro-inflammatory factor and inducer of TNF-alpha rele...

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According to the results, high-sensitivity C-reactive protein and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ (beetroot juice) compared with CB (cooked beets). FMD [flow-mediated dilation- blood vessel health] was significantly  increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were sig...

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TABLE OF REFERENCES

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https://pmc.ncbi.nlm.nih.gov/articles/PMC4877878/2.5Human studyAfter one month and 15 days of administration of beetroot-carrot juice therapy, the patient had improved appetite, a sense of general well-being and increased vigor daily activities. Furthermore, beetroot-carrot juice was used as an adjuvant to chlorambucil resulted in a substantial reduction in leukocytes and lymphocytes count in peripheral blood and improvement in the relevant biochemical parameters. Beetroot-carrot juice can be used as an effective treatment for CLL alone or in combination with chlorambucil when taken orally with regular diet on daily basis.Our novel therapy leads the postulation that natural food product with known anticancer activity as beetroot-carrot juice, when used in right combination and dose could enhance the therapeutic efficacy of the potent antileukmic drug chlorambucil, by reducing its toxic side-effects. A possible synergistic effect of consumption of beetroot-carrot juice with chlorambucil resulted in a substantial improvement in renal function by acting as a kidney cleanser and protects the patient from renal impairement. Furthermore, beetroot-carrot juice could be used as natural alternative treatment for CLL when it was daily consumed as it has an antileukemic and anticancer effect.
https://www.sciencedirect.com/science/article/pii/S0891584924005501#sec32Human studyCollectively, we observed that the consumption of concentrated nitrate-rich versus nitrate-depleted beetroot juice regularly for 4 weeks had a favourable effect on the oxLDL/NOx and GSH/GSSG ratios in middle-aged and older men and women with treated hypertension. The increased GSH/GSSG ratio, in particular, tentatively supports the concept that the regular intake of vegetable-derived nitrate modulates the redox balance within the blood circulation toward a less pro-oxidative profile.Another noteworthy observation was that, when compared with baseline, plasma hsCRP decreased following the daily consumption of 800 mg of nitrate-rich beetroot juice over 4 weeks (Fig. 4). High-sensitive CRP is an acute-phase protein that is used as an important marker of chronic systemic inflammation in nutritional intervention studies [58]. Epidemiological evidence suggests that diets rich in leafy green vegetables (as an important nitrate source) are inversely associated with plasma (hs)CRP levels
https://www.researchgate.net/publication/2859783752Human studyCollected data showed that ingestion of RBE for 10 days reduced [arthritis related metrics] in a time- and dose-dependent manner with maximum 33% reduction as compared to the first day of the treatment. Interestingly, due to the treatment, serum levels of TNF-alpha were reduced in subjects whose serum TNF-alpha was greater than 1 pg/mL prior to initiation of the treatment. It was also found that serum levels of AOPP (proteins oxidized by hypochlorous acid/hypochlorites) were reduced by up to 48% after 10 days of the treatmentAOPP is known as a pro-inflammatory factor and inducer of TNF-alpha release from monocytes. Therefore it was reasonable to verify whether treatment with RBE may result in reduction of blood TNF-alpha levels. In order to further investigate possible actions of betalains, sera from volunteers treated with RBE were subjected to a cytokine and chemokine array. In addition, it was found that treatment with RBE also resulted in reduction of blood level of IL-6, RANTES, and GRO-alpha.
https://www.nature.com/articles/jhh2016342Human study According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were significantly (P<0.05) decreased with RBJ or CBTotal antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB.
https://www.researchsquare.com/article/rs-1162429/v12Human studyThis trial suggests that daily administration of 24 ml concentrated beetroot juice decreases the concentrations of IL-6, TNF-α, and NF-κB which are involved in the pathogenesis of T2DM and its associated complications. To the best of our knowledge, this study is first to address the effects of concentrated BJ in ameliorating oxidative stress and inflammation in patients with T2DM. Since there are limited studies, more trials are warranted.This randomized controlled trial revealed that concentrated BJ consumption can improve some inflammatory markers in patients with diabetes. The significant improvement in three inflammatory markers including serum concentration of IL-6, and levels of TNF-α and NF-κB in PBMC resulted from 12 weeks of supplementation with BJ. The anti-inflammatory properties of beetroot have been demonstrated in several in vivo studies.
https://www.clinicalnutritionjournal.com/article/S0261-5614(24)00420-5/abstract1.5Human studyThose who ingested red beetroot juice had a greater abundance of bacteria with well-known beneficial effects, including Akkermansia, Oscillospira, Prevotella, Roseburia, Ruminococcaceae, and Turicibacter, compared with placebo. Participants allocated to beetroot juice supplementation were also characterized by significantly higher levels of fecal nicotinate, trimethylamine, and markers of beetroot juice intake (e.g., 5,6-dihydroxyindole)Beetroot juice supplementation for two weeks did not to induce significant improvements in functional outcomes in adults with long COVID compared with placebo. Beneficial effects were observed in both gut microbiota composition (i.e., increase in probiotic species) and inflammatory mediators.
https://www.dovepress.com/dietary-beetroot-juice--effects-in-patients-with-copd-a-review-peer-reviewed-fulltext-article-COPD1.5Human studyThe European Food Safety Authority (EFSA) has set the Acceptable Daily Intake (ADI) for nitrates and nitrites at 3.7 mg and 0.07 mg per kilogram of body weight, respectively.100,101 Similar to other clinical pharmacotherapies, nitrates have a specific dose-response range that defines their pharmacological activity. A dose that is too low may not reach the threshold to exert pharmacological effects, while exceeding a certain dose may lead to toxicological effects. In existing research on the impact of dietary beetroot juice on COPD [heart disease], most supplementation regimens involve 140 mL (12.9 mmol) of beetroot juice per day.46–48,50,52,57 Some studies have employed a regimen of 70 mL per instance, twice daily, in the morning and evening.19,45,58 Although not every study has yielded entirely positive results, the evidence suggests that a daily intake of approximately 140 mL of beetroot juice can significantly improve the exercise capacity, blood pressure, vascular function, and sleep quality of patientsour investigation furnishes invaluable reference for the utilization of beetroot juice in the treatment of COPD. Our review encompasses the metabolic pathways of dietary nitrates following the ingestion of beetroot juice and delineates the contributions of beetroot juice to various aspects such as exercise capacity, vascular function, blood pressure, and sleep in patients with COPD. Beetroot juice, as a natural dietary nitrate supplement, emerges as a favorable therapeutic alternative for patients who exhibit intolerance to exercise rehabilitation, antihypertensive medications, or sleep-improving drugs. Moreover, it may be synergistically coupled with other pharmacological treatments to enhance therapeutic outcomes. Nevertheless, there remain challenges to be addressed. The clinical phenotypic heterogeneity among COPD patients makes the diagnosis and treatment of COPD complex. Beetroot juice contains not only nitrates but also other bioactive constituents, whose roles in COPD are yet to be fully understood.
https://www.sciencedirect.com/science/article/pii/S030881462202951X#s00551.5Human study Compared to baseline, the study demonstrates transient changes in abundance of some taxa e.g., Romboutsia and Christensenella, after different days of intervention (p < 0.05). Enrichment of Akkermansia muciniphila and decrease of Bacteroides fragilis (p < 0.05) were observed after 3 days of juice consumption, followed by restoration in abundance after 14 days. With native betacyanins and catabolites detected in stool after juice consumption, betacyanins were found to correlate positively with Bifidobacterium and Coprococcus, and inversely with Ruminococcus (p < 0.1), potentiating a significant rise in (iso)butyric acid content (172.7 ± 30.9 µmol/g stool). Study findings indicate the potential of red beetroot to influence gut microbial populations and catabolites associated with these changes, emphasizing the potential benefit of red beetroot on intestinal as well as systemic health. Romboutsia and Bacteroidales) were observed, as well as enrichment of A. muciniphila and decrease in B. fragilis populations. A. muciniphila has been inversely associated with obesity, diabetes, inflammation, and metabolic disorders, whereas B. fragilis is potentially enterotoxigenic causing inflammatory diarrhea. Consumption of beetroot juice additionally increased the production of total SCFAs especially (iso)butyric acid in stools. Correlations between betacyanin variables and microbial taxa suggest a role of red beetroot pigments in modulating gut bacteria with putative health implications. Further research needs to assess the long-term implications of beetroot on the gut microbial changes including mucosal microbiota and the physiological consequences for the gut and the host organism.
https://www.sciencedirect.com/science/article/pii/S0022316622012883?via%3Dihub1.5Human studyThe main finding of this novel, randomized, controlled, crossover acute study was that consumption of nitrate-rich BB as a meal significantly increased endothelium-independent microvascular vasodilation in healthy, normotensive men compared with CB. In addition, significant reductions in DBP were observed postprandially after BB ingestion, which occurred in conjunction with significant increases in plasma and urinary nitrate and nitrite concentrations.In conclusion, we observed a significantly greater microvascular vasodilation response and lower DBP after acute consumption of BB compared with CB in healthy men and showed that dietary nitrate may be in part responsible for the effects. Moreover, bread containing beetroot may serve as an effective vehicle to increase consumption of cardioprotective beetroot in the diet. Further studies are needed to assess the long-term effects of beetroot ingestion on BP and vascular function, particularly in groups at risk of CVD.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4691670/1.5Human studyIn conclusion, this study supports the use of dietary nitrate as a safe, well-tolerated, and potentially powerful prevention strategy in CVD in individuals with early vascular dysfunction. This strategy is evidenced by improvements in FMD, vascular stiffness, and the platelet inflammatory profile. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment
https://www.sciencedirect.com/science/article/pii/S23523646203001581.5Human studyIn a randomised controlled trial, consuming whole beetroot for 8 weeks resulted in modification of risk factors for CVD and GIT disorders in older participants. Physical measures were unaffected and further assessment of more sensitive measures of functional performance are required to ascertain if whole beetroot may offer additional physiological benefits in older populations. Although the data here is promising, further mechanistic studies and larger clinical trials are required to confirm the findings.The beetroot group had a resting systolic BP reduction of 8.0 mmHg (p = 0.03), lower relative abundance of the phyla Bacteroidetes (p = 0.04), and a higher relative abundance of genus Alistipes (p = 0.03), increased Shannon diversity index (p = 0.03), fibre intake of 7 g/day (p < 0.01), nitrate intake 145 mg/day (p < 0.01), urinary nitrate of 460 μmol/L (p = 0.02) and SCFA concentrations (p < 0.05). However, 8 weeks of beetroot consumption did not have any impact upon functional measures, urine or plasma nitrate and BSS.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4425174/1Based on the available data, beetroot appears to be a powerful dietary source of health promoting agents that holds potential as therapeutic treatment for several pathological disorders. The powerful antioxidant, anti-inflammatory and vascular-protective effects offered by beetroot and its constituents have been clearly demonstrated by several in vitro and in vivo human and animal studies; hence its increasing popularity as a nutritional approach to help manage cardiovascular disease and cancer. In the human studies to date, beetroot supplementation has been reported to reduce blood pressure, attenuate inflammation, avert oxidative stress, preserve endothelial function and restore cerebrovascular haemodynamicsAs a source of nitrate, beetroot ingestion provides a natural means of increasing in vivo nitric oxide (NO) availability and has emerged as a potential strategy to prevent and manage pathologies associated with diminished NO bioavailability, notably hypertension and endothelial function. Beetroot is also being considered as a promising therapeutic treatment in a range of clinical pathologies associated with oxidative stress and inflammation. Its constituents, most notably the betalain pigments, display potent antioxidant, anti-inflammatory and chemo-preventive activity in vitro and in vivo.

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