Inflammation

A review of 56 randomized clinical trials found that psychotherapy may be effective in reducing inflammation. The trials included several different types of interventions, including cognitive behavior therapy (CBT), CBT plus medication, grief and bereavement support, a combination of two or more psychotherapies, and psychoeducation, among others. CBT was the best at boosting the immune system, followed by multiple or combined interventions. The benefits of CBT on the immune system lasted for at least six months following treatment.

https://www.eurekalert.org/pub_releases/2020-06/uoc--cbt060220.php

Shields GS, Spahr CM, Slavich GM. Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Psychiatry. Published online June 03, 2020. doi:10.1001/jamapsychiatry.2020.0431 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2766707

A mouse study explains why excessive weight around our middle affects cognition. It seems that such fat, known as visceral adiposity, generates high, chronic levels of a signal that encourages the formation of inflammasome complexes that amplify the immune response and inflammation.

A protein called NLRP3 is a core component of the inflammasome complex in the fat, and it’s what promotes the production and release of interleukin-1 beta by fat cells. When NLRP3 was blocked in mice, they became protected against such inflammation and cognitive problems. When visceral adipose tissue from obese mice and obese mice missing NLRP3 was transplanted into lean mice, the tissue from those missing NLRP3 had no deleterious effect, but the tissue from the intact obese mice caused increased levels of interleukin-1 beta in the hippocampus, and impaired cognition.

Mice missing interleukin-1 beta’s receptor on the microglia were also protected.

There are indications that interleukin-1 beta also prompts microglia to wrap around synapses, potentially interfering with the communication between neurons.

https://www.eurekalert.org/pub_releases/2020-03/mcog-vfd030220.php

Guo, D.-H., Yamamoto, M., Hernandez, C. M., Khodadadi, H., Baban, B., & Stranahan, A. M. (2020). Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells. The Journal of Clinical Investigation, 130(4), 1961–1976. https://doi.org/10.1172/JCI126078

A study measuring the levels of the six most common carotenoids in blood from 193 patients with coronary artery disease has found that lutein was the only carotenoid whose level was correlated with the inflammatory marker interleukin-6, IL-6. The higher the level of lutein in the blood, the lower the level of IL-6.

Cells taken from blood from patients with coronary artery disease confirmed that the inflammatory activity of the cells became significantly lower when they were treated with lutein.

Lutein is found in several highly coloured vegetables and fruits, and is particularly rich in vegetables with dark-green leaves, such as spinach.

https://www.eurekalert.org/pub_releases/2017-07/lu-vca070517.php

Chung, Rosanna W.S., Leanderson, Per, Lundberg, Anna K, Jonasson, Lena. 2017. Lutein exerts anti-inflammatory effects in patients with coronary artery disease. Atherosclerosis, 262, 87-93, published online 6 May 2017, doi: 10.1016/j.atherosclerosis.2017.05.008

Here are some nut studies that link to benefits in connection with diabetes, heart disease, and inflammation. However, it should be noted that they are often very small, and usually funded by nut organizations. I wouldn't put too much weight on such.

Nuts linked to improved type 2 diabetes health

A 3-month study involving 117 older adults (mean age 62) with diabetes found that 75g of nuts (½ a cup) a day, as a replacement for carbohydrate foods, can improve glycemic control and blood lipids in those with type 2 diabetes.

The nuts used were a mixed lot of tree nuts (almonds, Brazils, cashews, hazelnuts, pecans, pine nuts, pistachios, macadamias and walnuts) and peanuts. improved blood lipid levels and blood sugar levels in individuals with non-insulin dependent diabetes.

https://www.eurekalert.org/pub_releases/2018-05/mp-itn052218.php

Jenkins, D.J.A., C.W.C. Kendall, B. Lamarche, M.S. Banach, K. Srichaikul, E. Vidgen, S. Mitchell, T. Parker, S. Nishi, B. Bashyam, R. de Souza, C. Ireland, S.C. Pichika, J. Beyene, J.L. Sievenpiper, R.G. Josse, 2018. Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial. Diabetologia https://doi.org/10.1007/s00125-018-4628-9

Eating pecans had significant effect on biomarkers of heart disease and type 2 diabetes

A very small 4-week study involving 26 overweight and obese adults (average age 59) found that those given a diet with pecans substituted for 15% of the total calories significantly improved insulin sensitivity and had a significant effect on markers of cardiometabolic disease.

Both the control diet and the pecan-rich diet were low in fruits, vegetables and fiber.

https://www.eurekalert.org/pub_releases/2018-03/kc-n-eph032218.php

The study entitled "A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial" is available online and was presented at the American Society for Nutrition Annual Conference, Nutrition 2018 held in Boston in June.

A handful of nuts a day cuts the risk of a wide range of diseases

A review of 29 studies involving some 819,000 participants has concluded that people who eat at least 20g of nuts (a handful) a day have a 30% lower risk of heart disease, as well as lower risks of cancer, respiratory disease, and diabetes.

The study included all kinds of tree nuts, and also peanuts. The results were in general similar. There was little evidence of further improvement in health outcomes as a result of eating more than 20g of nuts.

Nuts and peanuts are high in fibre, magnesium, and polyunsaturated fats. Some nuts, particularly walnuts and pecan nuts are also high in antioxidants.

https://www.eurekalert.org/pub_releases/2016-12/icl-aho120216.php

[4526] McKay, D. L., Eliasziw M., Chen C. Y. Oliver, & Blumberg J. B.
(2018).  A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.
Nutrients. 10(3), 339.

Link between nut intake and inflammatory biomarkers

Data from 5,013 men and women participating in the Nurses' Health Study and Health Professionals Follow-up Study has revealed that higher nut intake (5 or more times per week) was associated with lower levels of inflammatory biomarkers (C-reactive protein (CRP) and Interleukin 6 (IL6)).

Research has also shown that nut consumption may be inversely related to body mass index (BMI), which is a strong determinant of inflammatory biomarkers, so it may be that the associations between nut intake and inflammatory markers are mediated in part through BMI.

http://www.eurekalert.org/pub_releases/2016-07/mp-itn072716.php

[4527] Yu, Z., Malik V. S., Keum NN., Hu F. B., Giovannucci E. L., Stampfer M. J., et al.
(2016).  Associations between nut consumption and inflammatory biomarkers.
The American Journal of Clinical Nutrition. 104(3), 722 - 728.

Initial findings from the Walnuts and Healthy Aging (WAHA) study indicate that daily walnut consumption positively impacts blood cholesterol levels without adverse effects on body weight among older adults.

The study involved 707 healthy older adults of whom some were told to add significant daily amounts of walnuts (~15% of caloric intake) to their usual diet. They were not given any advice on what they should be eating, apart from that.

After a year, a comparison of the two groups found that those eating the walnuts were not any heavier than those who hadn't included walnuts in their diet, but the walnut-diet resulted in significant reductions in LDL cholesterol. There was minimal effect on triglycerides and HDL cholesterol.

Another study reported at the conference found that daily consumption of 1.5 ounces of walnuts significantly affected the bacteria in the human gut in a way that was favorable to decreasing inflammation and cholesterol. This was a small study involving only 18 healthy adults. However, a 2015 study with rats similarly found that a diet with walnuts had a significant effect on gut bacteria communities.

Walnuts are unique among nuts in being primarily composed of polyunsaturated fat. This includes alpha-linolenic acid (ALA), the plant-based omega-3 fatty acid, which is known to reduce inflammation. Walnuts are the only nut that contain a significant amount of alpha-linolenic acid.

Walnuts are also said to be an excellent source of antioxidants — indeed, second only to blackberries.

http://www.eurekalert.org/pub_releases/2016-04/es-nri040116.php

Ros E, Rajaram S, Sala-Vila A, et al. Effect of a 1-Year Walnut Supplementation on Blood Lipids among Older Individuals: Findings from the Walnuts and Healthy Aging (WAHA) study [abstract]. FASEB J. 2016;30(Supp 1)293.4. Available at: http://www.fasebj.org/content/30/1_Supplement/293.4.abstract

Guetterman HM, Swanson KS, Novotny JA, et al. Walnut Consumption Influences the Human Gut Microbiome [abstract]. FASEB J. 2016;30(Supp 1)406.2. Available at: http://www.fasebj.org/content/30/1_Supplement/406.2.abstract

Vinson, JA & Cai, Y. (2012) Nuts, especially walnuts, have both antioxidant quantity and efficacy and exhibit significant potential health benefits. Food & Function, 3(2), 134-140 . http://pubs.rsc.org/en/Content/ArticleLanding/2012/FO/C2FO10152A#!divAbstract

A review of 200 studies on depression and inflammation has concluded that depression and inflammation fuel one another, with inflammation playing a key role in the development of depression in some people, and depression priming greater physiological responses to stress.

Moreover, depression that is caused by chronic inflammation is resistant to traditional therapy methods. However, it is more responsive to activities such as yoga, meditation, omega-3 fatty acids, NSAIDS and exercise.

The review indicates that treatment for depression needs to consider its pathway. The researcher suggests that chronic inflammation is most common in individuals who have experienced stress in their lives, including lower socio-economic status or those who experienced abuse or neglect as children. Other contributing factors are a high-fat diet and high body mass index.

If inflammation is a significant factor, it needs to be treated in tandem with the depression.

http://www.eurekalert.org/pub_releases/2015-12/ru-icf121815.php

Kiecolt-Glaser, J. K., Derry, H. M., & Fagundes, C. P. (2015). Inflammation: Depression Fans the Flames and Feasts on the Heat. American Journal of Psychiatry, 172(11), 1075–1091. http://doi.org/10.1176/appi.ajp.2015.15020152

Stress, including sleep disturbance, is a major contributor to inflammation in the body. Insomnia is associated with increased risk for depression, medical comorbidities, and mortality.

A study involving 123 older adults (55+) with insomnia randomly assigned them to one of 3 types of classes: cognitive behavioral therapy for insomnia, tai chi, or a sleep seminar (the control condition).

Cognitive behavioral therapy for insomnia reduced insomnia symptoms and levels of the inflammation marker C-reactive protein, and reversed activation of molecular inflammatory signaling pathways. These benefits were maintained for 16 months.

Tai chi also reduced inflammation, reducing the expression of inflammation at the cellular level and reversing activation of inflammatory signaling pathways. It marginally reduced levels of C-reactive protein. Again, these benefits were maintained for 16 months.

Those participants assigned to the sleep seminar classes showed no significant changes in inflammatory markers, as expected.

http://www.eurekalert.org/pub_releases/2015-11/e-bsa110515.php

Irwin, M. R., Olmstead, R., Breen, E. C., Witarama, T., Carrillo, C., Sadeghi, N., … Cole, S. (2015). Cognitive Behavioral Therapy and Tai Chi Reverse Cellular and Genomic Markers of Inflammation in Late-Life Insomnia: A Randomized Controlled Trial. Biological Psychiatry, 78(10), 721–729. http://doi.org/10.1016/j.biopsych.2015.01.010

Two experiments involving more than 200 young adults have indicated that the extent to which they experienced positive emotions (such as amusement, awe, compassion, contentment, joy, love and pride) was linked to lower levels of pro-inflammatory cytokines. In particular, awe, wonder and amazement, were associated with the lowest levels of the cytokine, Interleukin 6 (a marker of inflammation).

High levels of cytokines are associated with poorer health and such disorders as type 2 diabetes, heart disease, arthritis, and even Alzheimer’s disease and clinical depression.

It's suggested that awe is associated with curiosity and a desire to explore, behaviors which are the opposite of those found during inflammation, where individuals typically withdraw from others.

http://www.eurekalert.org/pub_releases/2015-02/uoc--ana020315.php

Stellar, J. E., John-Henderson, N., Anderson, C. L., Gordon, A. M., McNeil, G. D., & Keltner, D. (2015). Positive affect and markers of inflammation: Discrete positive emotions predict lower levels of inflammatory cytokines. Emotion, 15(2), 129–133. http://doi.org/10.1037/emo0000033

A study has revealed that the immune system has a seasonal cycle, in which its activity is boosted during the winter and relaxes during the summer. While the winter increase in immune defences presumably helps us stave off infections, it also raises the risk of harmful inflammation, effectively lowering the threshold for heart attacks, stroke, diabetes and even some psychiatric conditions. This may explain why deaths from conditions ranging from heart attacks to diabetes and schizophrenia increase in winter.

The study used blood samples from more than 16,000 people living in both the northern and southern hemisphere

http://www.theguardian.com/science/2015/may/12/winter-immune-boost-may-actually-cause-deaths-study-suggests

Dopico, X. C., Evangelou, M., Ferreira, R. C., Guo, H., Pekalski, M. L., Smyth, D. J., … Todd, J. A. (2015). Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nature Communications, 6, 7000. http://doi.org/10.1038/ncomms8000

Anecdotal and scientific evidence suggests curcumin, a compound found in turmeric, promotes health because it lowers inflammation. However, it is not absorbed well by the body. Most curcumin in food or supplements stays in the gastrointestinal tract, and any portion that's absorbed is metabolized quickly.

A new study thinks they've come up with a better and more effective way to deliver curcumin, and in so doing has demonstrated how it works. Curcumin powder was mixed with castor oil and polyethylene glycol, allowing it to dissolve and be more easily absorbed by the gut to enter the bloodstream and tissues.

When this was given to mice who had been injected with an extract that stimulates an immune reaction, a key protein that triggers an immune response was blocked. The mice given plain curcumin, on the other hand, showed the same protein actively triggering an immune response.

The emulsified curcumin also stopped recruitment of macrophages. Inflammation triggered by overactive macrophages has been linked to cardiovascular disease, disorders that accompany obesity, Crohn's disease, rheumatoid arthritis, inflammatory bowel disease, diabetes and lupus-related nephritis.

http://www.eurekalert.org/pub_releases/2014-11/osu-nra110614.php

A rat study has demonstrated that cytokines (immune system signaling molecules) impair communication among neurons in the hippocampus. The increased cytokine levels affected complex discrimination memory, that is, the ability to differentiate among generally similar experiences.

In the study, the rats were exposed to two similar environments, one of which was associated with a mild foot shock, making them reluctant to enter that environment. When some rats were then given a low dose of a bacterial agent to induce a neuroinflammatory response, leading to cytokine release in the brain, they became no longer able to distinguish between the two environments.

Analysis of changes in the activity patterns of hippocampal neurons suggested that cytokines impaired recall by disrupting the function of specific neuron circuits, taking the neural network that had learned the discrimination back to the state it had been before learning took place.

The finding may help explain "chemobrain", and suggests that an intervention aimed at reducing inflammation might be effective approach.

http://www.eurekalert.org/pub_releases/2014-09/uoc--bid091114.php

Czerniawski, J., & Guzowski, J. F. (2014). Acute Neuroinflammation Impairs Context Discrimination Memory and Disrupts Pattern Separation Processes in Hippocampus. The Journal of Neuroscience, 34(37), 12470–12480. http://doi.org/10.1523/JNEUROSCI.0542-14.2014

A Finnish study involving 2,570 middle-aged men (42-60) has found that men sleeping less than 6 hours or more than 10 hours suffer from low-grade inflammation (indicated by levels of C-reactive protein) more often than persons sleeping 7-8 hours per night. Additionally, the serum levels of zinc, and the zinc/copper ration, were lowest in those sleeping less than 6 hours, while copper levels were highest in those sleeping more than 10 hours.

It has been suggested that high serum copper concentration is linked to pro-oxidative stress, found in many chronic diseases.

http://www.eurekalert.org/pub_releases/2015-09/uoef-lsa091415.php

Luojus, M. K., Lehto, S. M., Tolmunen, T., Elomaa, A.-P., & Kauhanen, J. (2015). Serum copper, zinc and high-sensitivity C-reactive protein in short and long sleep duration in ageing men. Journal of Trace Elements in Medicine and Biology, 32, 177–182. http://doi.org/10.1016/j.jtemb.2015.07.008

A small clinical trial involving 49 older adults (average age 66) found that the group who were given a standardized mindfulness meditation program had greater improvement in sleep score than the group given a sleep hygiene education program. They also showed greater improvement on secondary measures of insomnia symptoms, depression symptoms, fatigue interference and fatigue severity. However, differences between the groups were not seen for anxiety, stress or inflammatory signaling, the last of which declined in both groups.

http://www.eurekalert.org/pub_releases/2015-02/tjnj-mma021215.php

Black DS, O’Reilly GA, Olmstead R, Breen EC, Irwin MR. Mindfulness Meditation and Improvement in Sleep Quality and Daytime Impairment Among Older Adults With Sleep Disturbances: A Randomized Clinical Trial. JAMA Intern Med. 2015;175(4):494-501. doi:10.1001/jamainternmed.2014.8081.

Mouse and human immune cells have demonstrated that a compound produced by the body when dieting or fasting (β-hydroxybutyrate — BHB) directly inhibits a protein, NLRP3, which is part of a complex set of proteins that drive the inflammatory response in several disorders, including autoimmune diseases, type 2 diabetes, Alzheimer's disease, atherosclerosis, and autoinflammatory disorders.

BHB is produced in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet.

The finding helps explain why calorie restriction reduces inflammation.

http://www.eurekalert.org/pub_releases/2015-02/yu-amo021315.php

Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., … Dixit, V. D. (2015). The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature Medicine, 21(3), 263–269. http://doi.org/10.1038/nm.3804

A meta-analysis of 61 controlled trials has concluded that consuming tree nuts, such as walnuts, lowers total cholesterol, triglycerides, LDL cholesterol, and ApoB, the primary protein found in LDL cholesterol. Walnuts were investigated in 21 of the 61 trials, more than any other nut reviewed.

Consuming at least two servings (two ounces) per day of tree nuts had stronger effects on total cholesterol and LDL. The evidence also suggests that tree nut consumption may be particularly important for lowering the risk of heart disease in individuals with type 2 diabetes.

Walnuts have also been shown to reduce inflammation, and improve arterial function.

http://www.eurekalert.org/pub_releases/2015-11/es-sft111815.php

Del Gobbo, L., Falk, M.C., Feldman, R., Lewis, K., Mozaffarian, D. Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis and dose-response of 61 controlled intervention trials. Am J Clin Nutr.2015; doi: 10.3945/ajcn.115.110965.

Kris-Etherton P. Walnuts decrease risk of cardiovascular disease: a summary of efficacy and biologic mechanisms. J Nutr. 2014; 10.39:2S-8S.

Zhao G, Etherton TD, Martin KR, et al. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 2004; 134: 2991-2997.

A British study involving 165 healthy nonsmoking adults (aged 40–70) has found that a diet based on UK health guidelines could reduce risk of a heart attack or a stroke by up to a third, compared to a traditional British diet

The predicted risk of cardiovascular disease over the next 10 years for the participants was estimated to be about 8% in the men and 4% in the women. Participants followed their diets for 12 weeks. Those on the modified diet ate oily fish once a week, more fruit and vegetables, replaced refined with wholegrain cereals, swapped high-fat dairy products and meats for low-fat alternatives, and restricted their intake of added sugar and salt. Participants were asked to replace cakes and cookies with fruit and nuts and were also supplied with cooking oils and spreads high in monounsaturated fat.

The average body weight in the group on the modified diet fell by 1.3 kg; that in the control group rose by 0.6 kg. Waist circumference was 1.7 cm lower in the dietary group compared to the control group. There were also significant falls in systolic blood pressure/diastolic blood pressure (4.2/2.5 mm Hg for daytime and 2.9/1.9 mm Hg for night time) and average heart rate. Cholesterol fell by 8%. High-sensitivity C-reactive protein (a marker for inflammation) was 36% lower. There was no significant change in markers for insulin sensitivity. Much of the fall in blood pressure could be accounted for by the drop in sodium.

http://www.eurekalert.org/pub_releases/2015-03/kcl-hdr031715.php

Reidlinger, D. P., Darzi, J., Hall, W. L., Seed, P. T., Chowienczyk, P. J., & Sanders, T. A. (2015). How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized controlled trial. The American Journal of Clinical Nutrition, 101(5), 922–930. http://doi.org/10.3945/ajcn.114.097352

A new study shows that a combination of inflammation and hypoxia activates microglia in a way that persistently weakens the connection between neurons, contributing to brain damage in conditions such as stroke and Alzheimer's disease.

http://www.eurekalert.org/pub_releases/2014-03/uobc-scb031214.php

[3625] Zhang, J., Malik A., Choi H. B., Ko R. W. Y., Dissing-Olesen L., & MacVicar B. A.
(2014).  Microglial CR3 Activation Triggers Long-Term Synaptic Depression in the Hippocampus via NADPH Oxidase.
Neuron. 82(1), 195 - 207.

A very large Italian study provides more evidence that the Mediterranean diet reduces inflammation, with their finding that those with a greater adherence to such a diet had significantly lower levels of platelets and white blood cells. These are both inflammatory markers: high platelet counts are associated with both vascular disease and non-vascular conditions such as cancer, and a high white blood cell count is a predictor of ischemic vascular disease.

http://www.eurekalert.org/pub_releases/2014-03/asoh-sfi033114.php

A mouse study has found that obese mice had high levels of interleukin 1 in both their blood and their brains, and this was associated with:

  • high levels of inflammation,
  • low levels of a biochemical important to synapse function, and
  • impaired cognitive function.

Moreover, when fat was removed from the obese mice, interleukin levels dropped dramatically, and cognitive performance improved.

Putting obese mice on an exercise program had a similar effect, even though they didn’t lose weight — but they gained muscle and lost fat.

http://www.fastcoexist.com/3027307/why-youre-fat/your-fat-is-why-youre-not-as-bright-as-you-could-be

Resveratrol — an ingredient in red wine that has been implicated in a number of health benefits — has been found to inhibit interleukin 6 (IL-6), a pro-inflammatory protein that is part of the immune system (although IL-6 can be anti-inflammatory during exercise). Resveratrol does this specifically through its effect on the estrogen receptor, preventing cell proliferation.

http://www.eurekalert.org/pub_releases/2014-04/sri-sfs042914.php

A 2-year trial involving 59 patients with type 2 diabetes has found that those on a low-carbohydrate diet showed lower levels of inflammation compared with those on a traditional low-fat diet. Weight loss was similar in both groups.

http://www.eurekalert.org/pub_releases/2014-05/lu-ldr050814.php

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