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Association of Retinol and Carotenoids Content in Diet and Serum With Risk for Colorectal Cancer: A Meta-Analysis.
Han, X, Zhao, R, Zhang, G, Jiao, Y, Wang, Y, Wang, D, Cai, H
Frontiers in nutrition. 2022;9:918777
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The incident rate of malignant tumours has been increasing, and so has colo-rectal cancer (CRC), which is now the third most frequent cancer and the second most common cause of cancer death. CRC development is influenced by environmental and genetic factors. Diet, diabetes, obesity, lack of physical activity, age, family history and history of benign adenomatous polyps and inflammatory bowel disease are all known risk factors. Modulating diet is one way to modify cancer risk. Vitamin A (retinol) and carotenoids, which are precursors to Vitamin A, are indispensable in the human body and widely occur in a range of vegetables, fruits and animal-derived foods. In some studies high dietary intake of retinol and carotenoids had been linked to a decreased risk of CRC, however, this was not consistent in all findings. To get a better understanding of this matter, the authors of this meta-analysis analysed 22 clinical studies from the last 20 years. The authors found an inverse association with carotenoids in blood serum, so higher blood serum of carotenoids seemed to decrease CRC risk. In regards to dietary intake, total carotenoid intake did not increase CRC risk and in fact the carotenoids carotenes, lycopene, and β-cryptoxanthin reduced risk, which was particularly noticeable in men. In women, high dietary intake of retinol also showed to reduce CRC risk, but it appeared to increase the risk in men. This raised the idea of gender-specific differences. Of clinical relevance are that carotenoids can be an important dietary contributors in reducing CRC risk. However the protective role of retinol appears to be gender-specific and only seems to benefit women, with the opposite effect in men.
Expert Review
Conflicts of interest:
None
Take Home Message:
The results of this study were mixed:
- Total dietary intake of carotenoids was not associated with CRC risk.
- Case control studies found that high serum carotenoids may increase CRC risk.
- There were differences in findings between males and females.
- Larger, well-controlled studies over long time frames are needed to further explore the relationship between dietary intake and serum concentrations of carotenoids and retinol with CRC. These studies should include results by sex, race and dose response.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Colorectal cancer (CRC) is the third most common cancer worldwide, and second in terms of mortality. Diet and environmental factors may have a strong influence and causative effect. Research has linked dietary consumption and serum levels of carotenoids and retinol with CRC. However, results have been mixed.
The aim of this meta analysis was to identify a potential association between CRC and carotenoid and retinol intake. A total of 22 cohort and case control studies published between 2000-2019 from across Europe, North America and Asia were included. The number of CRC cases totalled 19,293 from a sample of more than 450,000 people.
Eligible studies reported data in either relative risk (RR) or odds ratios (OR) with 95% confidence intervals (95% CI). In the meta analysis, data were combined and expressed as OR with 95% CI.
Cases and control groups were based on high or low carotenoid intake as defined by the included studies and based on dietary intake or serum concentration. Sub-group analysis was undertaken by study type, sex and tumour type. A sensitivity analysis tested the robustness of the results.
Due to the heterogeneity between studies, adjustments were made for potential covariates and confounding factors including age, gender, a family history of CRC, smoking, alcohol consumption and levels of physical activity.
The quality of the studies was assessed against predefined inclusion and exclusion criteria and scored using the Newcastle-Ottawa Scale (NOS).
The nutrients studied included; beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin and retinol. These were assessed through dietary intake or serum concentrations.
Key Findings
- High dietary intake of beta-carotene was not associated with an increased risk of CRC in females (OR = 0.97; 95%CI 0.79-1.19), however, it may lower CRC risk in males (OR = 0.74; 95% CI 0.55-0.99).
- High dietary intake of retinol was not associated with CRC risk (OR = 0.99; 95% CI 0.89-1.10). However, the findings suggested that it may reduce CRC risk in females but increase CRC risk in males.
- There was a tendency towards a slightly decreased risk of CRC with high dietary intakes of alpha-carotene), lycopene, and beta-cryptoxanthin. The results were more pronounced in males.
- No association was found between high consumption of high lutein/zeaxanthin, retinol or total carotenoids and the risk of CRC
- Case control studies found a negative association between serum carotenoids and CRC risk. This relationship was not found in cohort studies and therefore remains uncertain.
Conclusions
This was a well-conducted meta-analysis that was not subject to any conflicts of interest. Larger, well controlled prospective studies adjusting for sex and with long-term follow-up are needed to confirm the relationship between dietary intake and serum levels of carotenoids and CRC.
Notes: The authors had no conflicts of interest to disclose.
Clinical practice applications:
- Healthcare practitioners working with people with a family history of CRC or those who may be at increased risk may like to consider increasing carotenoid intake modestly.
- A modest increase in dietary intake of beta-carotene for males may be beneficial.
- A modest increase in dietary retinol may be beneficial for females.
Considerations for future research:
- Further research is needed to explore the differences between sexes for dietary intake of carotenoids and retinol and CRC risk
- Further studies are needed to investigate the relationship between serum carotenoids and CRC
- Analysis of results by race and continent may be beneficial
- Further research is needed to define dose response
- Due to heterogeneity between studies, large, well controlled studies over long time frames are needed
Abstract
Background: Colorectal cancer (CRC) risk is linked to serum and dietary retinol and carotenoids, according to clinical and epidemiological research. However, the findings are not consistent. As a result, we did this meta-analysis to determine the link between them. Methods: From 2000 through 2022, the PubMed, Web of Science, and Embase databases, as well as pertinent article references, were searched and filtered based on inclusion and exclusion criteria and literature quality ratings. High and low intake were used as controls, and OR (odds ratio) or RR (relative risk) and 95% confidence interval were extracted. The extracted data were plotted and analyzed using Stata12.0 software. Results: A total of 22 relevant studies were included, including 18 studies related to diet and 4 studies related to serum. For high and low intake or concentration controls, the pooled OR was as follows: β-carotene (OR = 0.89, 95% CI: 0.78-1.03), α-carotene (OR = 0.87, 95% CI: 0.72-1.03), lycopene (OR = 0.93, 95% CI: 0.81-1.07), lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87-1.07), β-cryptoxanthin (OR = 0.70, 95% CI: 0.48-1.01), total carotenoids (OR = 0.97, 95% CI: 0.81-1.15), retinol (OR = 0.99, 95% CI: 0.89-1.10), serum carotenoids (OR = 0.73, 95% CI: 0.58-0.93), serum retinol (OR = 0.62, 95% CI: 0.26-1.49). Subgroup analysis was performed according to tumor type, study type and sex. Conclusion: Total carotenoid intake and Lutein/Zeaxanthin intake were not associated with CRC risk. High β-carotene, α-carotene, lycopene, and β-cryptoxanthin all tended to reduce CRC risk. Serum carotenoid concentrations were significantly inversely associated with CRC risk.
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Higher circulating α-carotene was associated with better cognitive function: an evaluation among the MIND trial participants.
Liu, X, Dhana, K, Furtado, JD, Agarwal, P, Aggarwal, NT, Tangney, C, Laranjo, N, Carey, V, Barnes, LL, Sacks, FM
Journal of nutritional science. 2021;10:e64
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Diet has been identified as one of the important modifiable lifestyle factors in preventing Alzheimer’s disease. Carotenoids are potent antioxidants, naturally occurring pigments found in red, yellow, orange and dark green fruits and vegetables. Literature from epidemiological studies links fruit and vegetable consumption, and higher levels of carotenoids, with a lower risk of cognitive decline among older adults from different regions. The aim of this study was to examine (1) the association between dietary intakes of carotenoids and global/domain-specific cognition, and (2) how participants’ dietary patterns corresponded to their plasma levels of carotenoids. This study is an evaluation of baseline blood nutrients and cognition among the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) participants. Participants are predominantly Caucasian females with a mean age of 69⋅8 years. Results show that high levels of plasma α-carotene were associated with higher scores for global cognition, and episodic and semantic memory. The carotenoids lutein and zeaxanthin (combined) were positively associated with better scores for semantic memory. A dietary pattern that featured greater consumption of vegetables other than green leafy vegetables and fruits, corresponded to high α-carotene in blood which was associated with higher cognition scores. Authors conclude that blood nutrient levels as objective markers could characterise individuals’ dietary patterns, which could facilitate a targeted dietary intervention to prevent cognitive decline.
Abstract
There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.
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The Association between Diet and Hepatocellular Carcinoma: A Systematic Review.
George, ES, Sood, S, Broughton, A, Cogan, G, Hickey, M, Chan, WS, Sudan, S, Nicoll, AJ
Nutrients. 2021;13(1)
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Liver cancer is the sixth most common cause of cancer death in Australia. Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer. Obesity and diabetes are known risk factors for HCC development and so is the presence of liver cirrhosis, which can occur in hepatitis infections, dietary aflatoxins produced by certain moulds, excessive alcohol intake, tobacco smoking, and metabolic associated fatty liver disease. Emerging evidence recognises diet as a potential lifestyle-related risk factor in the development of HCC. This systematic review sought to determine whether there is an association between diet and the development of HCC by analysing 30 observational studies. Reduced risk in HCC development was seen in people who followed either a Mediterranean, Urban Prudent or Traditional Cantonese dietary pattern diet or ate according to the Alternative Healthy Eating Index-2010. Similarly, the intake of vegetables, whole grains, fish, poultry, coffee, plant-based compounds like isoflavones, macronutrients such as monounsaturated fats and micronutrients including vitamin E, vitamin B9, β-carotene, manganese and potassium were associated with reduced risk. Whereby sugar-sweetened beverages and processed red meat consumption appeared to increase HCC risk. This review found no particular impact concerning the DASH diet, nuts and fruit intake. Further discussed are also some of the potential mechanisms that some dairy products and omega-6 have on cancer and HCC risk. In conclusion, certain dietary patterns and diet components influence the risk of HCC development, thus affirming a dietary role in disease development and prevention. However, the impact on diet in high-risk individuals or those who already have HBV or cirrhosis remains to be studied further.
Abstract
Globally, liver cancer is the sixth most common cause of cancer mortality, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. Emerging evidence states that diet is recognised as a potential lifestyle-related risk factor for the development of HCC. The aim of this systematic review is to determine whether there is an association between diet and the development of HCC. Using the PRISMA guidelines, three databases (MEDLINE Complete, CINAHL and Embase) were systematically searched, and studies published until July 2020 were included. Thirty observational studies were selected. The protocol was registered with PROSPERO (CRD42019135240). Higher adherence to the Mediterranean dietary pattern, Alternative Healthy Eating Index-2010, the Urban Prudent Dietary Pattern, the Traditional Cantonese Dietary Pattern, intake of vegetables, wholegrains, fish, poultry, coffee, macronutrients such as monounsaturated fats and micronutrients such as vitamin E, vitamin B9, β-carotene, manganese and potassium were associated with a reduced risk of HCC. The results suggest a potential role of diet in the development of HCC. Further quantitative research needs to be undertaken within a range of populations to investigate diet and the relationship with HCC risk.
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Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.
Jenkins, DJA, Kitts, D, Giovannucci, EL, Sahye-Pudaruth, S, Paquette, M, Blanco Mejia, S, Patel, D, Kavanagh, M, Tsirakis, T, Kendall, CWC, et al
The American journal of clinical nutrition. 2020;112(6):1642-1652
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Oxidative damage is a shared characteristic in chronic diseases such as cardiovascular disease (CVD), diabetes, cancer and ageing. Antioxidants mitigate the impact of oxidants and have been widely investigated in ageing and disease. However, the evidence for supplementary antioxidants has been mixed and some authorities have advised against the use of certain single nutrients for the prevention of CVD or cancer. This systematic review and meta-analysis focused on selenium due to its vital role in the antioxidant system and associations of low selenium blood levels with increased risk of CVD, cancers and death. The study included 43 randomised controlled trials (RCTs) evaluating the effect of supplemental selenium and antioxidants with or without selenium and their impact on CVD risk, cancer and all-cause mortality. Overall supplemental selenium or antioxidants alone did not seem to be associated with CVD outcomes, cancer, CVD and cancer mortality, or all-cause mortality. On close examination, a decreased risk was seen for CVD mortality when antioxidants were combined with selenium, whilst antioxidant mixtures without selenium demonstrated an increased risk in all-cause mortality. The findings did not seem to be influenced by dietary selenium intake. The authors suggested that inclusion of selenium as part of an antioxidant mix could be key for an antioxidant associated risk reduction. However, in the absence of further long term studies, a balanced antioxidant-rich diet was advocated as the safest approach. In clinical practice, where antioxidant support beyond diet is warranted, supplemental antioxidant use should be concurrent with adequate selenium supplementation, with dose benefits of 50-200mcg observed.
Abstract
BACKGROUND Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.
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Improved antioxidant and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function.
Wood, LG, Fitzgerald, DA, Lee, AK, Garg, ML
The American journal of clinical nutrition. 2003;77(1):150-9
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Oxidative stress is elevated in patients with cystic fibrosis (CF). It has been hypothesised that supplementing with antioxidants reduces oxidative stress and therefore the rate of lung deterioration in CF patients. The aim of the study was to examine oxidative stress and antioxidant defences in CF patients after antioxidation supplementation in relation to fatty acid status, dietary intake and clinical status. Children with CF were given a high dose supplement containing 200mg vitamin E, 300mg vitamin C, 25mg beta-carotene, 90 micrograms selenium and 500 micrograms vitamin A for 8 weeks. The control group received low doses of vitamins A and E equal to the RDA, which is part of routine treatment for some CF patients. At the end of the study, the group taking the high dose antioxidant supplement showed significant increases in plasma concentrations of vitamin E, beta-carotene, selenium and glutathione peroxidase compared to the control group. Despite this, there were no significant differences in markers of lung function or wellbeing between the two groups. The researchers did however find correlations between both increased plasma fatty acids and antioxidant (beta-carotene and selenium) status and improved lung function, suggesting that antioxidant supplementation and high fat diets may be beneficial for CF patients. Since increased plasma fatty acids are linked to oxidative stress, the authors point out the importance of reducing oxidative stress in CF patients who are on a high-fat diet.
Abstract
BACKGROUND Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations. OBJECTIVE We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation. DESIGN Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation. RESULTS Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010). CONCLUSIONS Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.