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An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer.
Morze, J, Danielewicz, A, Przybyłowicz, K, Zeng, H, Hoffmann, G, Schwingshackl, L
European journal of nutrition. 2021;60(3):1561-1586
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The development of cancer is associated with a number of risk factors, including smoking, obesity, sedentary lifestyles, alcohol consumption, infections, pollution, and dietary imbalances. Based on previous research, optimal consumption of fruits, vegetables, and whole grains, along with reduced consumption of red and processed meat, reduces cancer risk. According to this systematic review and meta-analysis, adherence to the Mediterranean diet is associated with lower cancer mortality and site-specific cancer development. A Mediterranean diet includes fruits, vegetables, nuts, legumes, fish, whole grains, extra virgin olive oil, and low amounts of red meat, processed meat, egg, and dairy, along with moderate amounts of red wine. According to this systematic review and meta-analysis, adherence to the Mediterranean diet reduces the risk of cancer mortality and the risk of developing cancers specific to the site, such as colorectal cancer, bladder cancer, gastric cancer, and lung cancer. Among the components of the Mediterranean diet, fruits, vegetables, and whole grains have been shown to reduce cancer risk. Bioactive substances found in Mediterranean diet components require additional robust studies to evaluate their benefits. A healthcare professional can use the results of this study to make clinical decisions and recommend therapeutic interventions to cancer patients.
Abstract
PURPOSE The aim of current systematic review was to update the body of evidence on associations between adherence to the Mediterranean diet (MedDiet) and risk of cancer mortality, site-specific cancer in the general population; all-cause, and cancer mortality as well as cancer reoccurrence among cancer survivors. METHODS A literature search for randomized controlled trials (RCTs), case-control and cohort studies published up to April 2020 was performed using PubMed and Scopus. Study-specific risk estimates for the highest versus lowest adherence to the MedDiet category were pooled using random-effects meta-analyses. Certainty of evidence from cohort studies and RCTs was evaluated using the NutriGrade scoring system. RESULTS The updated search revealed 44 studies not identified in the previous review. Altogether, 117 studies including 3,202,496 participants were enclosed for meta-analysis. The highest adherence to MedDiet was inversely associated with cancer mortality (RRcohort: 0.87, 95% CI 0.82, 0.92; N = 18 studies), all-cause mortality among cancer survivors (RRcohort: 0.75, 95% CI 0.66, 0.86; N = 8), breast (RRobservational: 0.94, 95% CI 0.90, 0.97; N = 23), colorectal (RRobservational: 0.83, 95% CI 0.76, 0.90; N = 17), head and neck (RRobservational: 0.56, 95% CI 0.44, 0.72; N = 9), respiratory (RRcohort: 0.84, 95% CI 0.76, 0.94; N = 5), gastric (RRobservational: 0.70, 95% CI 0.61, 0.80; N = 7), bladder (RRobservational: 0.87, 95% CI 0.76, 0.98; N = 4), and liver cancer (RRobservational: 0.64, 95% CI 0.54, 0.75; N = 4). Adhering to MedDiet did not modify risk of blood, esophageal, pancreatic and prostate cancer risk. CONCLUSION In conclusion, our results suggest that highest adherence to the MedDiet was related to lower risk of cancer mortality in the general population, and all-cause mortality among cancer survivors as well as colorectal, head and neck, respiratory, gastric, liver and bladder cancer risks. Moderate certainty of evidence from cohort studies suggest an inverse association for cancer mortality and colorectal cancer, but most of the comparisons were rated as low or very low certainty of evidence.
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The impact of nutrition and lifestyle on male fertility.
Benatta, M, Kettache, R, Buchholz, N, Trinchieri, A
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2020;92(2)
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The impact of environmental, lifestyle and nutritional factors on unexplained male fertility has long been acknowledged. Yet, little research had been dedicated to the topic, despite declining semen quality having become a worldwide phenomena. Available studies have yielded limited, and at times conflicting, evidence. Hence this literature review sought to capture the current knowledge around unexplained male infertility and environmental, lifestyle, diet and nutrients factors. Summarized is the evidence from 69 studies, including population observations and clinical trials. The collected outcomes showed that a Western-type diet, rich in red and processed meats, refined grains, high-energy drinks and sweets, trans and saturated fats was associated with poor semen quality. Whereby higher intakes of fruits and vegetables, whole grains, omega-3 and poultry showed beneficial effects. However, as only selected groups were examined, more research is needed to project such findings onto the wider population. The reviewed evidence also included alcohol consumption, which showed high alcohol intake closely correlated to declining sperm concentrations. Whilst the verdict on caffeine consumption and the impact on sperm quality was inconclusive. In addition, several interventional studies evaluated the effect of dietary supplementation on various parameters of semen, where coenzyme Q10, L-carnitine, vitamin E, antioxidants, combined nutrient formulations and herbal blends all had positive outcomes. The review on zinc and folic acid supplementation yielded mixed results. This brief recap of the current evidence on environmental, lifestyle and nutritional influences on male infertility summarises the dietary foundations for the support of unexplained male infertility.
Abstract
BACKGROUND AND AIMS Male unexplained infertility has long been suspected to result from environmental, lifestyle and nutritional factors. However, the literature on the subject is still scarce, and clinical studies providing robust evidence are even scarcer. In addition, some similar studies come to different conclusions. Dietary pattern can influence spermatogenesis by its content of fatty acids and antioxidants. Yet, in an age of industrialized mass food production, human bodies become more exposed to the ingestion of xenobiotics, as well as chemicals used for production, preservation, transportation and taste enhancement of foods. We attempted in this paper to collect the available evidence to date on the effect of nutritional components on male fertility. MATERIAL AND METHODS A systematic search of the relevant literature published in PubMed, ScienceDirect and Cochrane Central Register of Controlled Trials Database was conducted. Literature was evaluated according to the Newcastle-Ottawa- Scale. RESULTS Epidemiological observations are concordant in demonstrating an association of low-quality sperm parameters with higher intake of red meat, processed and organ meat and fullfat dairy. On the contrary, better semen parameters were observed in subjects consuming a healthy diet, rich in fruit, vegetables, whole grains and fish. Evidences of the negative impact on male fertility of by-products of water disinfection, accumulation in food chain of persistent organochlorine pollutants, pesticides, phthalates from food and water containers and hormones used in breeding cattle have been reported. Clinical trials of the effects of micronutrients on semen parameters and outcomes of assisted fertilization are encouraging, although optimal modality of treatment should be established. CONCLUSIONS Although quality of evidence should be ameliorated, it emerges that environmental factors can influence male fertility. Some nutrients may enhance fertility whereas others will worsen it. With diagnostic analysis on a molecular or even sub-molecular level, new interactions with micronutrients or molecular components of our daily ingested foods and leisure drugs may lead to a better understanding of so far suspected but as yet unexplained effects on male spermatogenesis and fertility.
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Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study.
Kesse-Guyot, E, Rebouillat, P, Payrastre, L, Allès, B, Fezeu, LK, Druesne-Pecollo, N, Srour, B, Bao, W, Touvier, M, Galan, P, et al
The international journal of behavioral nutrition and physical activity. 2020;17(1):136
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The prevalence of type 2 diabetes (T2D) has significantly increased over recent decades, concomitantly to the obesity epidemic. Among the emergent risk factors, exposure to environmental contaminants including pesticides is of major concern. In fact, a recent European Food Safety Authority report indicated that 44% of conventional crop-based food contained at least one quantifiable pesticide residue, vs 6.5% in organic-labelled foods (OF). The aims of this study were (a) to investigate the prospective association between OF consumption and the risk of T2D, and (b) to estimate the mediation effect by the potential healthiness of a plant-based diet. This study is prospective cohort study based on the data from the web-based NutriNet-Santé study with an analysis sample of 33,256 participants. Results indicate an inverse association between organic plant-based food consumption and T2D risk especially in women. The association persisted after accounting for potential confounding effects of various factors, including lifestyles, dietary patterns and adiposity. Authors conclude that further studies are needed to replicate these findings for confirmation purposes and to elucidate underlying mechanisms.
Abstract
BACKGROUND Organic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors. The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D. METHODS A total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014-2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors). RESULTS During follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43-0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95-0.99). CONCLUSIONS In this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations. CLINICAL TRIAL REGISTRY The study was registered at ClinicalTrials.gov ( NCT03335644 ).
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A Systematic Review of Organic Versus Conventional Food Consumption: Is There a Measurable Benefit on Human Health?
Vigar, V, Myers, S, Oliver, C, Arellano, J, Robinson, S, Leifert, C
Nutrients. 2019;12(1)
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The demand for organic products has risen rapidly over the last decades. The reasons why consumers may favour organic over conventional products are varied. They may be for personal health and wellbeing, environmental considerations, animal welfare or perceived higher nutritional profile - which is true for some, but not all components. While the long-term safety of pesticide consumption through conventional food production has been questioned, organic foods clearly show lower levels of toxic metabolites, like heavy metals and synthetic fertilizer and pesticide residues. This systematic review aimed to assess the current evidence of organic diet consumption and human health compared to conventionally produced foods. Included were 35 papers on clinical trials and observational studies. The clinical trials studied pesticide and phytochemical excretion, antioxidant capacity, body composition, lipids and inflammatory markers. The observational studies were focused on fertility, foetal and childhood development, pregnancy, lactation and levels of pesticides in children and adults, as well as nutritional biomarkers and cancer risk in adults. An increased intake of organic produce in long-term studies appeared to reduce the incidence of infertility, birth defects, allergies, middle ear infection, pre-eclampsia, metabolic syndrome, high BMI, and non-Hodgkin lymphoma. Organic intake was also linked to reduced urinary levels of organophosphorus pesticides and herbicides. Yet, the author highlighted that organic consumers are more likely to be health conscious, physically active, eat a more plant-based diet, have higher education levels and income, and therefore are not representative of the general population. They also argue that the possible benefits from an organic diet may be partially due to the quality and composition of the diet rather than a direct effect of organic food consumption. Whereby a growing number of findings demonstrate the health benefits of organic food consumption, according to the authors, the current evidence does not yield a solid and definitive answer.
Abstract
The current review aims to systematically assess the evidence related to human health outcomes when an organic diet is consumed in comparison to its conventional counterpart. Relevant databases were searched for articles published to January 2019. Clinical trials and observational research studies were included where they provided comparative results on direct or indirect health outcomes. Thirty-five papers met the criteria for inclusion in the review. Few clinical trials assessed direct improvements in health outcomes associated with organic food consumption; most assessed either differences in pesticide exposure or other indirect measures. Significant positive outcomes were seen in longitudinal studies where increased organic intake was associated with reduced incidence of infertility, birth defects, allergic sensitisation, otitis media, pre-eclampsia, metabolic syndrome, high BMI, and non-Hodgkin lymphoma. The current evidence base does not allow a definitive statement on the health benefits of organic dietary intake. However, a growing number of important findings are being reported from observational research linking demonstrable health benefits with organic food consumption. Future clinical research should focus on using long-term whole-diet substitution with certified organic interventions as this approach is more likely to determine whether or not true measurable health benefits exist.
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Medical and Dietary Uses of N-Acetylcysteine.
Šalamon, Š, Kramar, B, Marolt, TP, Poljšak, B, Milisav, I
Antioxidants (Basel, Switzerland). 2019;8(5)
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N-Acetylcysteine (NAC) is an antioxidant naturally found in plants of the Allium species such as onions. As well as having antioxidant and anti-inflammatory properties, it is also needed to make glutathione which is an important antioxidant in cells. NAC has been used as a drug since the 1960s and is a popular dietary supplement. NAC is considered safe but the results of clinical trials are controversial or incomplete. This aim of this review is to provide a balanced view of further uses of NAC as a dietary supplement. It discusses the antioxidant properties in relation to conditions such as heart disease, diabetes and ageing; its medical uses, in the complementary treatment of cancer, as a sports supplement and as an anti-aging supplement. More information is needed on NAC and further clinical trials looking at its use in neurodegenerative diseases, addiction, and mental health disorders are underway. This may be relevant to the supplement users and may also help people suffering from chronic degenerative conditions.
Abstract
N-acetylcysteine (NAC), a plant antioxidant naturally found in onion, is a precursor to glutathione. It has been used as a drug since the 1960s and is listed on the World Health Organization (WHO) Model List of Essential Medicines as an antidote in poisonings. There are numerous other uses or proposed uses in medicine that are still in preclinical and clinical investigations. NAC is also used in food supplements and cosmetics. Despite its abundant use, there are projections that the NAC global market will grow in the next five years; therefore, the purpose of this work is to provide a balanced view of further uses of NAC as a dietary supplement. Although NAC is considered a safe substance, the results among clinical trials are sometimes controversial or incomplete, like for many other antioxidants. More clinical trials are underway that will improve our understanding of NAC applicability.
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Sorting out the Value of Cruciferous Sprouts as Sources of Bioactive Compounds for Nutrition and Health.
Abellán, Á, Domínguez-Perles, R, Moreno, DA, García-Viguera, C
Nutrients. 2019;11(2)
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Vegetable sprouts are naturally rich in nutrients and other beneficial compounds. The sprouts of cruciferous vegetables, such as broccoli, kale, radish and pak choi, stand out due to their high contents of glucosinolates and phenolic compounds. The aim of this review was to compile and update the available knowledge on the production, nutritional composition, and health benefits of cruciferous sprouts. A number of studies have found that compounds found in cruciferous sprouts have anti-cancer, anti-inflammatory, and antioxidant capacities. Consumption of cruciferous sprouts contributes to healthy glucose, insulin and fat levels in the blood, and may be beneficial for the treatment of some metabolic disorders, such as type 2 diabetes. There is evidence that compounds in cruciferous sprouts are a useful tool for enhancing phase II enzymes in the liver, and benefit levels of interleukine-6, C-reactive protein, and tumour necrosis factor-α, and inhibition of NF-κB, among others. The active compounds in these sprouts have an influence on several cardiovascular processes, potentially reducing the risk of several diseases. The lack of consistency between studies with regard to sampling schedules, doses, sample size, etc. means that it is not possible at this time to state the effective dose of sprouts or their active compounds needed in order to achieve health benefits. Further research is needed in this area.
Abstract
Edible sprouts with germinating seeds of a few days of age are naturally rich in nutrients and other bioactive compounds. Among them, the cruciferous (Brassicaceae) sprouts stand out due to their high contents of glucosinolates (GLSs) and phenolic compounds. In order to obtain sprouts enriched in these phytochemicals, elicitation is being increasing used as a sustainable practice. Besides, the evidence regarding the bioavailability and the biological activity of these compounds after their dietary intake has also attracted growing interest in recent years, supporting the intake of the natural food instead of enriched ingredients or extracts. Also, there is a growing interest regarding their uses, consumption, and applications for health and wellbeing, in different industrial sectors. In this context, the present review aims to compile and update the available knowledge on the fundamental aspects of production, enrichment in composition, and the benefits upon consumption of diverse edible cruciferous sprouts, which are sources of phenolic compounds and glucosinolates, as well as the evidence on their biological actions in diverse pathophysiological situations and the molecular pathways involved.
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Potential Factors Influencing the Effects of Anthocyanins on Blood Pressure Regulation in Humans: A Review.
Vendrame, S, Klimis-Zacas, D
Nutrients. 2019;11(6)
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Anthocyanins (ACNs) are plant compounds belonging to the flavonoid group of polyphenols and are naturally occurring in a number of foods. They are responsible for the red, blue and purple pigmentation within plant foods, such as blueberries and raspberries and are known to contain therapeutic compounds. Several studies have investigated the anti-inflammatory, antioxidant and blood pressure modulation properties within ACNs, however, results for blood pressure modulation, unlike those for anti-inflammatory and antioxidant properties have been mixed and less consistent. This paper reviews 66 human intervention trials exploring the effects of various forms of ACNs, like whole berries, concentrates and freeze-dried powders in order to identify the singular variables related to blood pressure modulation in order to further investigate. Having looked at a number of variables within the trials, researchers concluded that ACNs do in fact contain blood pressure lowering properties, but further research into varying factors including dose effect, synergistic effects, absorption and metabolism and the functionality of the individuals gut microbiota is needed to clarify results further.
Abstract
Dietary intake of anthocyanins (ACNs) is associated with a reduced risk of cardiovascular and coronary heart disease. While the anti-inflammatory, antioxidant, and lipid-lowering effects of ACN consumption have been consistently reported, their effect(s) on blood pressure regulation is less consistent and results from human studies are mixed. The objective of this review is attempting to identify potential patterns which may explain the variability in results related to blood pressure. To do so, we review 66 human intervention trials testing the effects on blood pressure of purified ACN or ACN-rich extracts, or whole berries, berry juices, powders, purees and whole phenolic extracts, from berries that are rich in ACN and have ACNs as predominant bioactives. Several factors appear to be involved on the mixed results reported. In particular, the baseline characteristics of the population in terms of blood pressure and total flavonoid intake, the dose and duration of the intervention, the differential effects of individual ACN and their synergistic effects with other phytochemicals, the ACN content and bioavailability from the food matrix, and individual differences in ACN absorption and metabolism related to genotype and microbiota enterotypes.
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The occurrence of resveratrol in foodstuffs and its potential for supporting cancer prevention and treatment. A review
Dybkowska, E, Sadowska, A, Świderski, F, Rakowska, R, Wysocka, K
Roczniki Panstwowego Zakladu Higieny. 2018;69(1):5-14
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There has been increasing interest in plant-based substances that show potential for preventing cancer development. Resveratrol is among these and is found in the skin of grapes, tomatoes and in red wine. Resveratrol displays anti-carcinogenic capacity by neutralising reactive oxygen species and modulating cell proliferation, differentiation and apoptosis. The purpose of this review was to present the characteristics of resveratrol as a bioactive compound and assess the mechanism of its anti-cancer properties. According to many in vitro and in vivo studies, resveratrol is able to inhibit all stages of carcinogenesis in several types of cancer. Based on these findings, the authors conclude there is a need to promote knowledge of the beneficial effects of resveratrol, and that conventional cancer treatment should be supported by an increase of this substance from both foodstuffs and supplements.
Abstract
Over recent years, there has been increasing interest noted in those active substances derived from plants that show potential for preventing cancer development. The most promising candidate is resveratrol which can be found in large amounts in the skin of grapes, tomatoes and in red wine. Its beneficial effects on the human body are seen both in prevention and therapy. The anti-carcinogenic action of resveratrol is linked with its ability to neutralise reactive oxygen species and to modulate cellular processes such as apoptosis, and both cancerous cell proliferation and differentiation. This article presents the characteristics of resveratrol as a bioactive compound derived from natural sources exhibiting anti-cancer properties, which, because of a wide spectrum of biological activities may be used in the prevention of cancer. Many in vitro and animal-based studies have demonstrated such preventative anti-cancer action in the colon, prostate, breast and lungs. The beneficial effects of resveratrol are also presented when adopted as a support to conventional treatments of cancer using chemo- and radio-therapy.
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Anti-Obesity Effects of Medicinal and Edible Mushrooms.
Ganesan, K, Xu, B
Molecules (Basel, Switzerland). 2018;23(11)
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Medicinal mushrooms have long been considered healthful due to of their anti-oxidant and anti-inflammatory properties, such as high-quality proteins, polyunsaturated fatty acids, polyphenols etc. More recently they have been analysed for their anti-obesity effects. The health implications of obesity are extensive, often affecting all bodily systems. The purpose of this review was to analyse previous animal studies to determine whether consuming edible mushrooms has a positive effect on obesity related illnesses, such as Type 2 diabetes and cardiovascular disease etc. The authors explore and summarise the different methods used to treat obesity including pharmacotherapy (weight loss drugs), natural products such as Ayurveda medicine and exercise. They present promising results that suggest the therapeutic properties of edible mushrooms have anti-obesity potentials and propose that the findings from animal studies could likely be mirrored in humans and recommend consuming mushrooms to aid weight loss and therefore improve health.
Abstract
Obesity is a group of metabolic disorders caused by multiple factors, including heredity, diet, lifestyle, societal determinants, environment, and infectious agents, which can all lead to the enhancement of storage body fat. Excess visceral fat mass in adipose tissue generate several metabolic disorders, including cardiovascular diseases with chronic inflammation based pathophysiology. The objective of the current review is to summarize the cellular mechanisms of obesity that attenuate by antioxidant potentials of medicinal and edible mushrooms. Studies have showed that mushrooms potentially have antioxidant capacities, which increase the antioxidant defense systems in cells. They boost anti-inflammatory actions and thereby protect against obesity-related hypertension and dyslipidemia. The practice of regular consumption of mushrooms is effective in the treatment of metabolic syndrome, including obesity, and thus could be a good candidate for use in future pharmaceutical or nutraceutical applications.
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The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder.
Delhey, LM, Nur Kilinc, E, Yin, L, Slattery, JC, Tippett, ML, Rose, S, Bennuri, SC, Kahler, SG, Damle, S, Legido, A, et al
Journal of clinical medicine. 2017;6(2)
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Primary mitochondrial disease and secondary mitochondria disorders have received increasing recognition in the medical world. In fact, mitochondrial dysfunction plays a significant role in many common illnesses such as diabetes, obesity, cancer and heart disease, as well as neurologic and psychiatric conditions. Yet less is known about the optimal treatment for mitochondrial disorders. Given the scarcity of clinical research, current treatment is mostly based on expert opinions, preclinical trials and animal models. Autism spectrum disorder (ASD) is a neurological and developmental condition that manifests in divergent behaviours affecting learning, communication and social engagement. Recent research suggests that there may be a link between mitochondrial abnormalities and ASD. About half of children with ASD display measurable biomarkers indicative of mitochondrial dysfunction, and the prevalence of primary mitochondrial disorders is much higher in children with ASD compared to those without ASD presentation. Several mitochondrial co-factors are supplemented in the management of mitochondria disease and also have shown promising effects on ASD symptoms. Hence this observational study sought to explore the impact of such substances on mitochondrial function in children with ASD. The project involved 127 children with ASD, some subjects were on specific mitochondrial supplements and some also had a diagnosed mitochondrial disease. The activity of mitochondrial metabolism was assessed at several stages, via a salivary mouth swab. Results from this study suggested that several common mitochondrial supplements such as fatty acids, antioxidants, B12 and folate influence mitochondrial function. However, some of these influences were more pronounced or in some cases limited to the subgroup that also had prevailing mitochondrial disease. The findings affirm that these interventions improve mitochondrial function and maybe be most effective in ASD cases with underlying metabolic disorders.
Abstract
Treatment for mitochondrial dysfunction is typically guided by expert opinion with a paucity of empirical evidence of the effect of treatment on mitochondrial activity. We examined citrate synthase and Complex I and IV activities using a validated buccal swab method in 127 children with autism spectrum disorder with and without mitochondrial disease, a portion of which were on common mitochondrial supplements. Mixed-model linear regression determined whether specific supplements altered the absolute mitochondrial activity as well as the relationship between the activities of mitochondrial components. Complex I activity was increased by fatty acid and folate supplementation, but folate only effected those with mitochondrial disease. Citrate synthase activity was increased by antioxidant supplementation but only for the mitochondrial disease subgroup. The relationship between Complex I and IV was modulated by folate while the relationship between Complex I and Citrate Synthase was modulated by both folate and B12. This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities. Measurements of mitochondrial activity that can be practically repeated over time may be very useful to monitor the biochemical effects of treatments.