Dr Dingle's Blog / wellness
Growing up as a child in the 60’s there was lots of space to play on the street, in the big back yards, nearby parks, creeks, the beach and lots of green spaces. While we we have lost a lot of these spaces research is showing that the more “green” we are surrounded with the the healthier it is for us. We exhibit more than just a preference for natural scenes and settings; we suffer health problems when we lose contact with our green surrounds. Increasing evidence indicates that nature provides restorative experiences that directly affect people's physical, social and mental well-being and health in a positive way including decreased mortality.
A recent study found that living in more densely vegetated areas was associated with fewer deaths from causes other than accidents. Using data from the Nurses’ Health Study researchers estimated a 12% lower rate of non-accidental death between women who lived in the most densely versus least densely vegetated areas. When looking at specific causes of death, the researchers estimated a 41% lower rate of kidney disease mortality, a 34% lower rate of respiratory disease mortality, and a 13% lower rate of cancer mortality in the women who lived in the greenest areas, compared with those in the least green areas. A study in the Netherlands found a lower prevalence of diseases in areas with more green space, including coronary heart disease and diabetes. In a cross-sectional study of 11,404 adults in Australia the odds of hospitalization for heart disease or stroke was 37% lower, and the odds of self-reported heart disease or stroke was 16% lower, among adults with highly variable greenness around their home, compared to those in neighborhoods with low variability in greenness. The odds of heart disease or stroke decreased by 7% per unit with every 25% increase in the level of greenness. In an interesting experiment where 14 children undertook two, 15 min bouts of cycling at a moderate exercise intensity while in one situation viewing a film of cycling in a forest setting and another with no visual stimulus. The systolic blood pressure (the top or higher number) 15 minutes after exercise was significantly lower following green exercise compared to the control condition. So if it works for kids it should also work for us we get older.
The rise in obesity is well documented and while there are many contributing factors a systematic review of green space research from sixty studies reported the majority (68%) of papers found a positive association between green spaces and obesity-related health indicators. One study found that increased vegetation was associated with reduced weight among young people living in high population densities and across eight European cities, people were 40% less likely to be obese in the greenest areas. Overall, the majority of studies found some evidence of a relationship with weight and green space. The lower rates of obesity, adverse health and improved health outcomes may be attributable to higher levels of physical activity, such as neighborhood walking which is positively influenced by the natural environment. Walking is the most popular physical activity particularly as we age, and levels of recreational walking have been linked the distance to and attractiveness of local parks and ovals. Many studies have reported that adults with access to a large high-quality park within walking distance (within 1600 m) from home have elevated levels of walking and and in general live longer. In a review of 50 studies twenty studies (40%) reported a positive association between green space and physical activity, including older adults.
Being around vegetation can lead to better mental health and less stress, positive emotions, focus and attention, as well as reduced stress. While walking itself can reduce stress, walking in a natural setting provides greater stress-relieving benefits. Accessible green spaces are ‘escape facilities’, and lack of access to green space contributes to poor mental health. Some of the more potent restorative effects of nature relate to being able to ‘get away’ from everyday settings and immerse oneself in an extensive natural setting that creates a sense of being in a ‘whole other world’.
Perhaps as we decide to age healthier we need to spend more time near green spaces.
Another reason to add some of the cabbage family to your daily diet, preferably raw is because of their gut healing properties and how they promote gut health through the gut microbiome. The Brassica family including cabbage, broccoli, brussel sprouts, kale, arugula (rocket), bok choy, cauliflower, collard greens, radish, turnip and others have been recognized for their gut healing and gut health properties for hundreds of years and modern epidemiologic studies have shown a frequent consumption of cruciferous vegetables is associated with lower risk of cancer, especially cancers of the digestive tract, bladder, breast, prostate, and lung. However, only now are we recognizing that many of these benefits are mediated through the microbiome and that their frequent consumption alters the composition of the microbiome.
Cruciferous vegetables are a rich source of glucosinolates a precursor to the Isothiocyanates (ITC), which exhibit powerful biological functions in fighting cancers, cardiovascular, neurodegenerative diseases and gut healing. The Isothiocyanates are a by product of specific plant enzymes (myrosinase) active during chewing or crushing when broccoli is consumed raw or lightly steamed, however, like all enzymes myrosinase is deactivated by cooking and ingestion of cooked broccoli typically provides only about one tenth the amount of isothiocyanates as that from raw broccoli. So to maximize the gut healing, gut health and overall benefits of these foods they are best eaten raw or just lightly steamed.
Instead when cooked cruciferous vegetables are consumed, gut bacteria are mainly responsible for ITC production in the gut. This is highlighted after taking oral antibiotics, the ITC’s availability and uptake decreases after eating cooked cruciferous vegetable. It also appears that there is considerable difference in the ability of individuals, due to individual differences in gut microbial community, to produce the isothiocyanates. Although, the gut community’s ability is altered over just 4 days. In one study feeding raw or cooked broccoli for four days or longer both changed the microbiota composition and caused a greater production of isothiocyanates. Interestingly, a three-day withdrawal from broccoli reversed the increased microbial metabolites suggesting that the microbiota requires four or more days of broccoli consumption and is reversible.
The lactic acid bacteria appear to have myrosinase-like activity and the fermented Brassica food products, such as sauerkraut and kimchi, are particularly rich in Lactobacillus, and a diet rich in Brassica may promote Lactobacillus growth in the colon.
Despite what we are often told the overwhelming evidence shows that Type 2 diabetes is a diet and lifestyle illness. It also shows that when you reverse the conditions that caused it the disease is also reversible.
Type 2 diabetes (T2D) is a chronic disease closely linked to the epidemic of obesity that requires long-term medical attention to limit the development of its wide range of complications. Many of these complications arise from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion. Approximately 10% of the population of the USA and Canada have a diagnosis of T2D, and the morbidity and mortality rates associated with it are fairly high. The economic burden of T2D in the USA is $245 billion and around $20 billion in Australia.
This case documents three patients referred to the Intensive Dietary Management clinic in Toronto, Canada, for insulin-dependent type 2 diabetes. It demonstrates the effectiveness of therapeutic fasting to reverse their insulin resistance, resulting in cessation of insulin therapy while maintaining control of their blood sugars. In addition, these patients were also able to lose significant amounts of body weight, reduce their waist circumference and also reduce their glycated haemoglobin level.
These three cases exemplify that therapeutic fasting may reduce insulin requirements in T2D. Given the rising cost of insulin, patients may potentially save significant money. Further, the reduced need for syringes and blood glucose monitoring may reduce patient discomfort.
Therapeutic fasting has the potential to fill this gap in diabetes care by providing similar intensive caloric restriction and hormonal benefits as bariatric surgery without the invasive and dangerous surgery. During fasting periods, patients are allowed to drink unlimited amounts of very low-calorie fluids such as water, coffee, tea and bone broth. A general multivitamin supplement is encouraged to provide adequate micronutrients. Precise fasting schedules vary depending primarily on the patient’s preference, ranging from 16 hours to several days. On eating days, patients are encouraged to eat a diet low in sugar and refined carbohydrates, which decreases blood glucose and insulin secretion.
This means that patients with T2D can reverse their diseases without the worry of side effects and financial burden of many pharmaceuticals, as well as the unknown long-term risks and uncertainty of surgery, all by means of therapeutic fasting.
Despite the increases in technology, life style changes and the promise of more free time, it is becoming apparent that stress is becoming one of the greatest health concerns of the Western World. Recent statistics indicate that between 70 ‑ 80 percent of all health related problems are either precipitated or aggravated by stress. Although the way we live, and the situations we face everyday have changed over thousands of years, our modern brain still has the ability (as it has had for thousands of years) to give us the same feelings and responses to stress. This is because these are deeply instinctive responses of protection and survival.
‘Distress’ is stress that arises from a negative situation such having an argument, being under too much pressure at work, or being called into the bosses office. ‘Eustress’ on the other hand, is stress that results from a positive situation, such as getting married or receiving an award . A mild amount of pressure can be beneficial; making a person more motivated to increase performance. However, the major difference between the positive eustress and the negative distress is how you perceive them. To one person public speaking creates eustress but to another it creates distress and high pressure for one individual in the work environment may not be experienced by another, being instead seen as more of a personal challenge. They both place the same physiological demands on the body, but are processed mentally and emotionally in different manners.
However, too much pressure or pressure for a long period of time can lead to excessive stress, a state of distress, which is unhealthy for both the mind and body. Stress can also be looked at from being acute and chronic stress.The evolutionary explanation behind stress is that ancestor’s perceived reaction to threats and dangers has survival value. When hunter-gathers would risk their lives in hunting for food or defending their community they would experience dangers that would trigger the bodies stress response, preparing them for action, to either fight or flee from the threat. In today’s society, stress experienced is not usually life threatening but still triggers the same stress response.
The reason I call it the blood pressure smoothie is all of the ingredients have been shown in many scientific studies to reduce blood pressure. By no way is this meant to replace advice from you GP but you can share it with them and see if they are interested in preventing the problem rather than just treating it with pharmaceuticals. Remember also that I am not a GP I am just the guy who does all the research which is why I have a PhD.
4 ingredients in order of importance
Almonds (soaked for at least 8 hours)
Filtered re-mineralised ionized water.
Extras for taste and minerals
Start by grinding the linseed and the almond in the smoothie maker.
Add the beetroot and the filtered water to make up to the constituency you need.
If you want to make it a bit sweeter add some ripe banana, dates or coconut water (and coconut meat if you have the whole coconut) as they are rich in Potassium (and other minerals) which is essential for muscle relaxation and tastes great. But wait till the banana is ripe for the best taste. You can also cold green tea instead of water to add to the antioxidant mix.
The properties that make this smoothie such a potent blood pressure mix is all of the ingredients have excellent antioxidant properties, rich in minerals and other nutrients liked with lowering blood pressure in scientific studies.
High blood pressure or hypertension is having a blood pressure reading of above of around 90mm Hg on 140mm Hg. Hypertension itself is not a disease but a condition or as an indicator of ‘increased risk’ of cardiovascular disease. Patients who are hypertensive have an increased risk of heart attack and stroke due to the direct correlation between the two. Hypertension also contributes significantly to the increased risk of kidney failure and other chronic illness.
In healthy people the cells of blood vessels produce the substance called nitric oxide (NO) which instructs smooth muscles surrounding arteries to relax. If they cant relax they stay rigid and you end up with high blood pressure. The NO is produced in a single layer of cells that line the inside of the arteries called the endothelium. If this tissue is damaged in the case of too much pressure, oxidation or through other means it stops producing NO and blood pressure rises.
Many of the beneficial actions of nutrition on lowering blood pressure results both directly and indirectly through improving endothelial tissue and NO production and release from this tissue. Two major pathways to increase NO are increase the rates of nitrates in the diet, the building block for NO, and L-Arginine which stimulate the enzyme to manufacture NO. Endothelial-derived NO also inhibits platelet adhesion, activation, secretion, and aggregation and promotes platelet disaggregation so you are less likely to have a stroke. A third mechanism that is absolutely critical is to protect and repair the endothelium, remember it is only one cell thick and very susceptible to damage. Vitamin C and antioxidants are essential for this part.
Diets high in dietary nitrate such as beetroot are associated with reduced blood pressure increased exercise performance as a result of vasodilation (expansion) of the blood vessels and a decreased incidence in cardiovascular disease. 100-200mg of beetroot per day has been shown to produce immediate effects of lowering blood pressure by around 15 mm of Hg. Beetroot is also rich in vitamins, phytochemicals and contains large amounts of iron and folic acid Mg, Na and Ca. Apart from the nitrates the major bioactive molecules in beet are polyphenols, flavonoids, betalains, therapeutic enzymes, ascorbic acid, and dehydroascorbic acid (DHAA). So they not only provide the ingredients for NO production but also help in repair and protection of the endothelium.
Almonds have one of the highest sources of L-Arginine (most nuts have lots of L-Arginine so you can substitute the almonds if you want) which stimulates NO synthesis. Studies of almonds have shown reductions of 5-6 mm of blood pressure. It is important to soak the almonds as they (all nuts and seeds) have enzyme-inhibiting factors in them which stop them from germinating until they have enough water. These enzyme inhibitors also stop the absorption of some nutrients, particularly minerals. When you soak the nuts many of the nutrients also become more available for digestion.
Flaxseed is rich in Omega 3 fatty acids, L Arginine (about 20% less than almonds), lignans, antioxidants and fiber that together probably provide benefits to patients with cardiovascular disease. Studies on consuming 30g of flaxseed have been shown to reduce blood pressure by up to 15 mm Hg.The great thing about this smoothie is that you can add just about anything else you want to it and it will make it even tastier and better for you.
A short time between eating your last meal and sleep can increase your risk of breast and prostate cancer.
One of the most important factors in regulating our gut health, digestion and controlling our microbiome is the pH or acid level.
While often mentioned in terms of the stomach, the pH has a controlling role to play in the health of the entire GI tract from the mouth to the anus; changes in the “normal” pH anywhere in the gut can have major implications on the rest of the GI tract. The pH scale goes from 1, being very acidic, to 14, being very alkaline. The level in our blood and tissues should be constantly around 7.36, neutral, and the level in our GI tract varies from 1 to 8. We cover this a lot more in our book Overcoming Illness, which focuses on the role of inflammation, oxidation and acidosis in illness.
After initial breakdown by chewing, food is churned by the smooth muscles of the stomach and is broken down by hydrochloric acid and stomach juices (enzymes). The pH of the stomach is highly acidic, around 1.5 (1.0 to 2.5) due to the hydrochloric acid that helps to kill harmful micro-organisms, denature protein for digestion, and help create favourable conditions for the enzymes in the stomach juices, such as pepsinogen. Not to mention sending messages along the GI tract that everything is working well in the stomach. If the pH is too high, say 3 or 4 (low acidity and more alkaline), then the system does not work and you end up with poor gut health, digestive and health complications. For example, premature infants have less acidic stomachs (pH more than 4) and as a result are susceptible to increased gut infections. Similarly, the elderly show relatively low stomach acidity and a large number of people, more than 30%, over the age of 60 have very little or no hydrochloric acid in their stomachs.
Similarly, in gastric bypass weight loss surgery, roughly 60% of the stomach is removed. A consequence of this procedure is an increase in gastric pH levels that range from 5.7 to 6.8 (not 1.5) making it more alkaline and, as a result, more likely to experience microbial overgrowth. We see similar patterns in other clinical cases such as acid reflux in which treatment involves the use of proton-pump inhibitors and celiac disease where delayed gastric emptying is associated with reduced acidity and increased disease.
Unfortunately, acid reflux is often wrongly treated as a condition that involves the production of too much acid. It is, in fact, the stomach finding it difficult to digest the foods, most commonly as a result of not having enough acid to complete digestion. Medications (see my other posts) which further reduce stomach acid have serious and sometimes deadly side effects on health, the digestive process and the gut microbiota. Acid reflux affects about 20% of the adult population and is much higher in older people, which is consistent with studies showing lower stomach acid as we age.
 Adbi 1976; Martinsen et al., 2005.
 Carrion and Egan, 1990.
 Husebye et al., 1992.
 Machado et al., 2008.
 Amir et al., 2013.
 Usai et al., 1995.
While antibiotics have been lifesaving, the over-prescription of antibiotics has sparked the evolution of drug-resistant strains of life threatening bacteria, resulting in tens of thousands of deaths each year. The US Centers for Disease Control estimate that up to 50% of antibiotics prescribed in the US are unnecessary. Unfortunately, the use of antibiotics is often prescribed for those groups who are more vulnerable to dysbiosis, including infants born via C-section and in those born preterm, compared to term infants born vaginally, potentially compounding the problems. Micro-organisms such as bacteria, fungi, viruses, and parasites cause many of the world’s diseases, yet only bacterial infections are usually susceptible to treatment with commonly prescribed antibiotics.
However, more subtle side effects of antibiotics on the gut microbiome are only just beginning to be discovered. Broad-spectrum antibiotics can impact up to 30% of the bacteria among the human microbiota, resulting in severe loss of species and function and begins immediately following antibiotic administration. The effects can sometimes last for years after its cessation, and may also lead to the total extinction of some beneficial microbial species. As few as three days of treatment with the most commonly prescribed antibiotics can result in sustained reductions in microbiota diversity. A typical two-week course of high-dose antibiotic treatment, as might be used for an ear infection, can wipe out most of the beneficial gut microbes.
These antibiotic-induced changes in the microbiota have been linked to many disease states including increased infections, metabolic disturbances, obesity, autoimmunity, and mental health conditions. Common outcomes of antibiotics the antibiotic-disturbed gut microbiota are diarrhea and infections with Clostridium difficile, particularly in infants.
Early life exposure to antibiotics presents the greatest risk of long-term damage to the gut microbiota and the more you take, the worse it is. In young children, antibiotics may change the development of the “adult” microbiota, and not allow its normal maturation. It has also been hypothesized to cause a delay in microbial maturation from six to 12 months after birth. Early life exposure is also associated with numerous diseases later in life including IBD, obesity, and asthma, as well as the development of immune-mediated metabolic and neurological diseases.
In a meta-analysis of eight studies including 12,082 subjects, antibiotic use in the first year of life was significantly associated with two-fold (200%) increased chance of the child having asthma. One study reported the use of antibiotics in newborns increased the risk of developing asthma by 24 times. Probiotics during the neonatal period were protective and reduced the risk by as much as 86% for childhood asthma for kids at risk. Studies of mice treated with antibiotics in early life revealed altered microbial populations within the gut microbiota and consequently increased the susceptibility of these mice to asthma.
Antibiotic use has also been shown to have long-term effects on brain neurochemistry and behavior. Such use is known to alter the intestinal microbiome with subsequent changes in microbiota to gut-brain axis and result in poorer neuro-cognitive outcomes later in life.
Even treatment with a single antibiotic course was associated with a 25% higher risk for depression and the risk increased with recurrent antibiotic exposures to 40% for two to five courses and 56% for more than five courses of antibiotics. The higher the rates of antibiotic use, the higher the rates of depression. Animal studies have shown that high doses of a cocktail of antibiotics induced lasting changes in gut microbiota associated with behavioural alterations.
Animal studies of early life exposure to antibiotics show lasting immune and metabolic consequences. Administration of low doses of penicillin to mice early in life increases the risk of weight gain and obesity and promotes lipid accumulation by altering the gut microbiota. Mice treated continuously with low-dose penicillin from one week before birth until weaning exhibited higher body weight and fat mass in adulthood, although the microbial structure returned to normal after four weeks of antibiotics cessation. There is also evidence of antibiotics playing a role in the development of IBD in children and that antibiotic usage during the first year of life was more common in those diagnosed with IBD later in life.
In human studies, mother’s use of antibiotics during pregnancy is consistently associated with cow’s milk allergy, wheeze, asthma, and atopic dermatitis, with the strongest association for antibiotic use in the third trimester of pregnancy. A study of 306 children with asthma showed that mother’s use of antibiotics during pregnancy increased the risk by a whopping four times (390%). Low-dose penicillin in late pregnancy and early postnatal life in the offspring of mice resulted in lasting effects on gut microbiota, increased brain inflammation, and resulted in anxiety-like behaviours and displays of aggression. Similar results have been shown for antibiotic exposure through breastfeeding.
"Gut Secrets" the book
Gut health tour dates
Gut Health, Gut Healing Australia. facebook group
 Fleming-Dutra et al., 2016.
 Fleming-Dutra et al., 2016.
 Penders et al., 2006.
 Forsgren et al., 2017.
 Francino, 2016.
 Jakobsson et al., 2010.
 Shira et al., 2016.
 Francino, 2016.
 Ng et al., 2013.
 Rousseau et al., 2011.
 Fouhy et al., 2012; Tanaka et al., 2009.
 Bokulich et al., 2016.
 Ibid, 2016.
 Hviid et al., 2011.
 Azad et al., 2014.
 Metsälä et al., 2013.
 Arrieta et al., 2014.
 Marra et al., 2006.
 Zhang et al., 2017.
 Russell et al., 2012.
 Rogers et al., 2016; Tochitani et al., 2016.
 Russell et al., 2013.
 Lurie et al., 2015.
 Bercik, P. et al., 2011; Desbonnet, L. et al., 2015; Fröhlich, E. E. et al., 2016; Wang, T. et al., 2015.
 Russell et al., 2013; Cox et al., 2014.
 Cox et al., 2014.
 Ibid, 2014.
 Shaw et al., 2010; Ortqvist et al., 2017.
 Shaw et al., 2010.
 Chu et al., 2015.
 Stensballe et al., 2013; Kashanian et al., 2017; Mulder et al., 2016; Murk et al., 2011.
 Timm et al., 2017.
 Zhao et al., 2015; Wang et al., 2017.
 Zhang et al., 2017.
 Leclercq et al., 2017.
 Kummeling et al., 2007.
Depression itself is not a disease, but a symptom of an underlying problem. A new theory called the “Immune Cytokine Model of Depression” holds that depression is a “multifaceted sign of chronic immune system activation,” inflammation. Depression may be a symptom of chronic inflammation. And a large body of research now suggests that depression is associated with a low-grade, chronic inflammatory response and is accompanied by increased oxidative stress—not a serotonin imbalance.
Researchers discovered in the early 1980s that inflammatory cytokines produce a wide variety of psychiatric and neurological symptoms that perfectly mirror the defining characteristics of depression. Cytokines have been shown to access the brain and interact with virtually every mechanism known to be involved in depression including neurotransmitter metabolism, neuroendocrine function, and neural plasticity.
This is now supported by increasing lines of scientific evidence including:
- Depression is often present in acute, inflammatory illnesses.
- Higher levels of inflammation increase the risk of developing depression.
- Administering endotoxins that provoke inflammation in healthy people triggers classic depressive symptoms.
- One-quarter of patients who take interferon, a medication used to treat hepatitis C that causes significant inflammation, develop major depression.
- Up to 50% of patients who received the cytokine IFN-alpha therapy to help treat cancer or infectious diseases developed “clinically significant depression.”
- An experiment involving the administration of a Salmonella typhi vaccine to healthy individuals produced symptoms of fatigue, mental confusion, psychomotor slowing and a depressed mood. These symptoms correlated with the increase in cytokine concentrations.
- Remission of clinical depression is often associated with a normalization of inflammatory markers.
- There is now a large body of literature regarding laboratory animals demonstrating that cytokines … can lead to a host of behavioural changes overlapping with those found in depression. These behavioral changes include decreased activity, cognitive dysfunction and altered sleep.
- All the activities associated with reducing the prevalence of depression and depression symptoms are anti-inflammatory. These include increased sunlight and time spent outside, exercise and physical activity, relaxation and meditation techniques, healthy eating as well as administering anti-inflammatory nutritionals.
There is further support from large epidemiological studies. A number of longitudinal studies have now shown that inflammation in early adulthood predicts depression at a later stage in life. In a large longitudinal study, the risk for depression and psychotic experiences in adolescence was almost two-fold higher in individuals with the highest compared to the lowest levels of inflammation as indicated by interleukin-6 (IL-6) levels in childhood. Children who were in the top third of IL-6 levels at the age of 9 years were 55% more likely to be diagnosed with depression at the age of 18 than those with the lowest childhood levels of IL-6. Children in the highest level of IL-6 levels at the age of 9 were also 81% more likely to report psychotic experiences at the age of 18. A study of more than 73,000 men and women showed increasing inflammation levels were associated with increasing risk for psychological distress and depression. Increasing inflammation (CRP) levels were also associated with increasing risk for hospitalization with depression.
In support of the inflammation depression link, recent studies have found a significant link between the dietary inflammatory index (DII) and risk of depression. In an Australian study of 6,438 middle-aged women, those with the most anti-inflammatory diet had an approximately 26% lower risk of developing depression compared with women with the most pro-inflammatory diet. Similarly, a study in the UK examined the DII and recurrent depressive symptoms over five years in 3,178 middle-aged men and 1,068 women. Researchers found that for each increment of 1 level of DII score (increased inflammation), odds of depression increased by 66% in women, whereas in men the risk increased by only 12%. In a study of 15,093 university graduates in Spain, those on the highest DII (strongly pro-inflammatory diet) had a 47% risk of depression compared with those in the bottom, with a significant dose-response relationship, which means as the diet became more inflammatory it increased the risk of depression. Further analysis also showed the association between DII (the inflammatory diet) and depression was stronger among participants older than 55 years, with an increased risk of 270% and those with cardiometabolic comorbidities (high blood pressure, diabetes, etc.) had an 80% increased risk of depression. In a study of 43,685 women (aged 50–77) without depression at baseline, the risk of developing depression was 41% higher if they were on the highest compared to the lowest Dietary Inflammatory Index diet.
Oxidative stress is closely related to the inflammatory pathway in particular. Pro-inflammatory cytokines are produced in reaction to oxidative stress and oxidative stress in turn amplifies the inflammatory response. High cortisol levels have been associated with increased levels of oxidative damage. Depression has been associated with increased oxidative stress and increased severity of depression is associated with increased systemic oxidatively generated DNA and RNA damage. Severe depression is associated with increased systemic oxidatively generated RNA damage, which may be an additional factor underlying the somatic morbidity and neurodegenerative features associated with depression. In a meta-analysis, 1,308 subjects depressed persons had increased oxidative stress and decreased anti-oxidant defences (as measured by 8-OHdG and F2-isoprostanes). The results indicate that depression is associated with increased oxidative damage to DNA and lipids. The brain is particularly vulnerable to oxidative damage due to its high oxygen consumption and low antioxidant defences. Sustained oxidative brain damage during a depressive episode may make a sufferer prone to developing another depressive episode. Therefore, it has been hypothesized that exposure to oxidative stress could be an explanatory mechanism in the remitting and chronic course of depressive disorders. There is also evidence from post-mortem studies suggesting that in depression oxidative stress is increased and antioxidants are decreased in the brain.
A study of 37 patients with bipolar disorder showed that bipolar disorder is associated with increased oxidatively generated damage to nucleosides, which could be contributing to the increased risk of medical disorders, shortened life expectancy, and the progressive course of illness observed in bipolar disorder. Another study showed increased oxidative stress as indicated by increased nitric oxide (NO) and lipid peroxidation, measured by thiobarbituric acidic reactive substance (TBARS) assay in patients with bipolar disorder.
There is evidence suggesting that antioxidants are decreased in depression, illustrated by lower antioxidant levels, including carotenoids, and antioxidant enzymes. There is some evidence to suggest that antidepressants have antioxidant properties and may act through reducing pro-inflammatory cytokines and ROS production and improving levels of antioxidants such as superoxide dismutase.
 Miller et al. 2009.
 Berk et al. 2011.
 Miller 2009.
 Brydon et al. 2008.
 Dantzer et al. 2008.
 JAMA Psychiatry 13, 2014.
 Wium-Anderson et al. 2013.
 Nitin Shivappa et al. 2016 British Journal of Nutrition.
 Akbaraly et al. Clinical Psychological Science 2016.
 Sanchez-Villegas A et al. British Journal of Nutrition 2015.
 Lucas et al. 2014.
 Joergensen et al. 2011.
 Jorgensen et al. 2013; Pandya et al. 2013.
 Black et al. 2014; Palta et al. 2014.
 Moylan et al. 2013.
 Wange et al. 2009; Michel et al. 2012.
 Gawryluk et al. 2011.
 Munkholm et al. 2015.
 Andreazza et al. 2008.
 Palta et al. 2014.
 Milaneschi et al. 2012.
 Sarandol et al. 2007.
 Khanzode et al. 2003; Lee et al. 2013.