In his book Blindspots, Marty Makary MD (slated to be the next FDA commissioner) discusses why routine medical practices are often slow to change, despite mounting evidenced that those practices are not supported by best evidence. Although not discussed in his book, the evaluation and treatment of hypothyroidism presents a prime example of this problem. Before diving into the issues, lets review some basic physiology.
The hypothalamus in the brain produces TRH (thyrotropin releasing hormone) in response to circulating levels of T3 and T4 (two forms of thyroid hormone). TRH then stimulates production and release of TSH (thyroid stimulating hormone) in the pituitary gland. In turn, TSH stimulates the thyroid gland to produce thyroid hormone. The two forms of thyroid hormone produced by the thyroid gland are called T4 and T3 (T3 has 3 iodine molecules, T4 has 4) T4 is the predominant hormone produced by the thyroid gland. In the liver and the kidney T4 is converted to T3 through a process called deiodination, supplying 80% of circulating T3. Importantly, T3 is 7 to 10 times more potent than T4.
When testing thyroid function, most physicians order only TSH (thyroid stimulating hormone) and T4. But to have normal thyroid function several conditions must be met. Of those many conditions, three are often not considered by most physicians and not evaluated with TSH and T4. First, there must be adequate conversion of T4 into T3, because T3 is the form of thyroid hormone that provides most physiologic effect. Second, there must be adequate transport of T4 and T3 into your cells. Third, levels of reverse T3 should not be high enough to block adequate amounts of Thyroid Hormone binding to receptors on your cells.
The “normal” range of TSH in most labs is 0.4 to 5.0 mU/L. Recently a narrower range of 0.5-2.5 mU/L has been proposed to exclude individuals with “minimal” thyroid dysfunction, but this is controversial. This controversy is the crux of one of the many problems in interpreting “normal” thyroid function tests. Proponents of the narrower range maintain that patients with symptoms of hypothyroidism and a TSH above 2.5 might benefit from treatment. In addition, proponents of the narrower range suggest that some patients with TSH levels above 2.5 may not report symptoms of hypothyroidism but their physiology may be suboptimal for health. (https://www.ncbi.nlm.nih.gov/books/NBK278958/) Physiology of the Hypothalamic-Pituitary-Thyroid Axis.
Treatment with T4 alone, may not provide adequate thyroid replacement.
T3 and T4 enter the hypothalamus and pituitary glands “passively”, meaning an active transport mechanism is not necessary. But in the rest of the body active transport of T3 and T4 into cells is necessary. If there is a problem with the active transport system, the hypothalamus and pituitary may “see” normal levels of T3 and T4 but the rest of the body may not be getting the full benefit of thyroid hormone. Thus, TSH levels will be normal, T4 levels will be normal, but cellular T3 and T4 levels will not be adequate. Yet physicians will interpret a normal TSH and T4 to mean normal thyroid function. Conditions that impair thyroid hormone transport into cells include: insulin resistance, diabetes, obesity, chronic and acute dieting, diabetes, depression, anxiety, bipolar disorder, neurodegenerative diseases, chronic fatigue syndrome, fibromyalgia, cardiovascular disease, inflammation and chronic illness, and disorders of lipid metabolism.
Therefore, in addition to problems with deiodinase (conversion of T4 to T3), high levels of reverse t3 can render monotherapy with levothyroxine inadequate, while leaving TSH and T4 levels “normal”.
This has been a quick discussion of a complex system. Not all aspects of thyroid testing and treatment have been addressed. Hopefully this discussion will help you understand why simply measuring TSH and T4 (a common practice) will not tell you whether you have normal thyroid function. Ideally, all patients being tested would have free T3 and reverse T3 measured in addition to T4 and TSH. In addition, the free T3/reverse T3 ratio and the free T3/freeT4 ratio would be considered when deciding whether treatment with T4 alone (levothyroxine monotherapy) is adequate. Many patients would benefit from adding T3 (triiodothyronine) to T4 (levothyroxine) therapy. In addition, a TSH level above 2.5 should be carefully evaluated for hypothyroid symptoms as levels above 2.5 are arguably “abnormal” (or at least should raise a red flag as to the possibility). Finally, recognize that this discussion presents controversies in medicine. Most practitioners apply the concept of “sick euthyroid” to patients with acute illness and low T3 levels, considering it a “normal” protective mechanism that does not require thyroid hormone therapy. But under chronic conditions, many practitioners who think “outside the box” would consider poor conversion of T4 to T3 and/or high levels of reverse T3, as possible indications for thyroid hormone therapy when symptoms of hypothyroidism are present. Under these circumstances directly addressing underlying causes such as chronic inflammation may provide the best initial approach. (anti-inflammatory diet, regular exercise, good sleep habits, stress reduction, strengthen social support)
But when a patient is already on monotherapy with T4, consideration of adding T3 to improve quality of life and physiologic function is worthy of consideration when comprehensive laboratory evaluation suggests problems as described above (cellular transport, T4 to T3 conversion, high reverse T3).
For a greater dive into this subject follow these links.
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“The promising findings coming from the cumulative research work over the last decade solidified the role of ω-3 PUFAs as a potential candidate to prevent or even treat such autoimmune diseases as type 1 diabetes, RA, SLE, MS”
“Altogether the data reported in this review show that anti-inflammatory interventions, i.e., high fish consumption or supplements containing n-3 PUFAs, should be the standard of care, along with pharmacotherapy, in treating patients with RA.”
And here is a graphic from that article showing the effect of SPMs (specialized pro-resolving mediators, derived from omega-3s):
Some omega-3 supplement studies have demonstrated no significant pain relief in osteoarthritis. Those studies did not reduce the consumption of pro-inflammatory n-6 fatty acids which compete with omega-3 fats for the enzymes which can lead to pro or anti-inflammatory mediators. They also did not measure the omega 6/omega 3 ratio in blood or tissues. Nor did they measure the omega-3 index (% of omega-3 achieved in red blood cell membranes, the gold standard for evaluating tissue levels achieved) This 2018 analysis stated:
“High Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with lower levels of inflammatory mediators, anti-nociception, and adaptive cognitive/emotional functioning. High Omega-6 (n-6) PUFAs are associated with inflammation, nociception, and psychological distress. While findings related to n-3 supplementation in knee OA are mixed, consideration of the n-6:n-3 ratio and additional outcome measures may provide improved understanding of the potential relevance of these fatty acids in OA”
The authors went on to access blood n-6/n-3 ratios in patients with OA and found the following:
“The high ratio group reported greater pain and functional limitations, (all p’s<0.04), mechanical temporal summation (hand and knee, p<0.05), and perceived stress (p=0.008) but not depressive symptoms.”
“In adults with knee pain, a high n-6:n-3 ratio is associated with greater clinical pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared to a low ratio group.”
The anti-inflammatory diet that I follow and recommend eliminates the major sources of excess omega-6 in the diet, specifically the “vegetable oils” which are actually seed, grain, and legume oils predominated by soy oil, corn oil, peanut and cottonseed oil present in cooking “vegetable oils” and processed foods. A table that displays the ratio of omega 3 to omega 6 in various oils can be found here. Note that this table does not reveal the amounts of MUFA (mono unsaturated fatty acids) which are arguably “heart healthy”. Nor does it address the important issue of protective polyphenols and anti-oxidants (such as in Extra Virgin Olive oil aka EVOO). So do not make choices of oil based only on the omega-3/6 ratio.
Another consideration in choosing oils for cooking (as opposed to salad dressing) is the smoke point. Under high heat, oils are subject to oxidation which creates a proinflammatory effect when consumed. Refined Avocado oil has the highest smoke point (520 degrees F). But we digress. Back to pain and arthritis.
“omega-3 polyunsaturated fatty acids (PUFA) have demonstrated an influential role in the progression of OA, resulting in the reduction of cartilage destruction, inhibition of pro-inflammatory cytokine cascades, and production of oxylipins that promote anti-inflammatory pathways.”
“Research has demonstrated a positive effect on the modulation of OA symptoms through diet and exercise to promote an anti-inflammatory environment. More specifically, omega-3 PUFAs have demonstrated a reduction in inflammatory biomarkers and cartilage degradation, counteracting the natural disease state of OA. In addition to their chondroprotective role, omega-3 supplementation has been shown to have indirect positive effects on muscle tissue recovery following exercise, which is necessary to prevent the progression of OA and maintain an independent, healthy lifestyle. The effects of omega-3 supplementation on the disease state of OA and its symptoms remain inconclusive. Further clinical trials utilizing human participants are warranted to provide a conclusive recommendation on standardized supplementation of omega-3 for the modulation of osteoarthritis.”
Given the cardioprotective effects, discussed in my last post (including an 80% reduction in sudden death at the highest quintile of omega-3 index) and other benefits (reduction in all cause mortality with high tissue levels), there are many reasons to include large amounts of low mercury fatty fish (wild Alaskan salmon, sardines, herring, trout) in the diet and to consider supplementation when your omega 3 index is < 8%. Likewise, in the presence of arthritis and pain, getting tissue levels of omega 3 up and reducing excessive pro-inflammatory omega 6 will likely provide significant benefit.
Here is a graphic with the omega 3 content of some foods.
And another:
As mentioned in my previous post about omega-3 and cardiovascular health, 1800 mg of omega-3 FA daily is adequate in most people to achieve and omega-3 index of 8%, the level at which cardiovascular protection is greatest.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
The benefit of omega-3 supplementation has been debated in the cardiology and nutritional literature for many years. Most studies of supplementation have failed to measure tissue levels achieved and often used very low doses. But when tissue levels were measured, either in the serum or red blood cell membrane, the studies consistently demonstrated significant reductions in all-cause mortality and cardiovascular mortality associated with high levels of omega-3 fatty acids.
In addition, higher levels of omega 3 are associated with >=80% reduction in sudden death associated with acute myocardial infarction (acute MI) and > 80% reduction in sudden death in cohorts without known coronary artery disease followed long term.
Two Coronary CT Angiogram (CCTA) studies demonstrated that patients with stable coronary artery disease on statin therapy randomized to high dose EPA and DHA had “prevention of coronary plaque progression when an omega-3 fatty acid index >= 4% was achieved.”
Another CCTA study demonstrated that patients receiving omega 3 supplementation had significantly less coronary atherosclerotic “high risk” lipid rich plaque prevalence (3.8% versus 32%) and lower total non-calcified plaque burden independent of cardiovascular risk factors compared to matched controls not receiving omega 3 supplements.
Omega 3 supplementation after an acute myocardial infarction has been found to reduce infarct size, reduce scaring (fibrosis), and enhance heart tissue healing. (Randomized controlled clinical trial) However a post MI study in 1027 elderly patients randomized to receive 1.8 grams per day of EPA+DHA versus a control group receiving corn oil showed no reduction in the primary composite cardiovascular endpoint between the two groups at 2 years but a higher incidence of AF in the omega 3 group that did not reach statistical significance.
Recently a study, widely reported by the lay press, suggested that high dose omega-3 supplementation was associated with increased risk of atrial fibrillation (AF). These results conflicted with previous studies which demonstrated just the opposite, specifically prior studies demonstrated reduced risk of AF. The more recent study suffered a significant design flaw. The study in question failed to make statistical adjustment for the increased life span associated with higher levels of omega-3. Since age is a primary risk factor for AF, any intervention which increases life span would be expected to result in more AF over the lifetime of the patients as they aged (i.e., more elder years results in increased risk of AF). Therefore, statistical adjustment for that effect should be employed, but was not done in the study.
Unfortunately, science journalism has deteriorated to a state where the conclusions of study authors are most often quoted without interpretation or context, and without critical analysis or comparisons with previous studies that may have demonstrated opposing results.
In addition to large well-designed studies that have suggested a reduced risk of AF associated with omega-3 fatty acids, there have been natural experiments that provide reassuring information. The indigenous Inuit people of Greenland, for example, historically consumed large amounts of omega-3 in their diet with no evidence of increased risk of AF. In fact, before the introduction of western processed foods, estimates of AF among the Inuit were 0.6% (1963) compared to a “worldwide prevalence of AF in adults between 2 and 4%, between one and two percent in Canadian and the general US population and between 0.5% and 3% in most low- and middle-income countries.” A more recent study of Greenland yielded a prevalence of 1.4% likely reflecting a change in habits consisting of less exercise, more tobacco use and a shift to a more Western diet.
Still, multiple studies that used high dose omega 3 supplements in patients with known cardiac disease suggest an increased risk of AF. A good review of omega-3 fatty acids and atrial fibrillation was published in the Korean Journal of Internal Medicine, referenced below.
My interpretation of the complex data in this area is as follows.
At supplemental doses of EPA+DHA above 1.8 grams per day (and perhaps above 1 gram per day) in patients with known coronary artery disease (CAD), at high risk of CAD, or following a myocardial infarction, the risk of AF is increased by about 25% (relative risk). But the risk of lethal ventricular arrythmias (sudden death) associated with myocardial infarction (heart attack) is 80% lower in patients with a red blood cell omega 3 index of >=8. In people without known CAD, an omega-3 index >=8% is associated with an 80% reduction in sudden cardiac death. CCTA studies show significantly lower unstable “vulnerable” plaque in patients on omega-3 supplements. Similarly, omega 3 supplementation in patients on statins associates with halted plaque progression determined by serial CCTA in non-diabetics.
In addition, higher tissue levels of omega 3 are associated with significantly reduced all-cause, cardiovascular, and cancer mortality.
Omega-3 fatty acids are the chemical precursors of SPMs, specialized pro-resolving lipid mediators which help resolve inflammation. We know that cardiovascular events are driven by chronic inflammation in the walls of arteries, often mediated by insulin resistance. Chronic inflammation contributes to atherosclerosis (production of plaque in the artery wall) as well as cardiovascular events that result when unstable plaque ruptures. Studies suggest that n-3 fatty acids may have antiarrhythmic properties with membrane-stabilizing effects in addition to antithrombotic and anti-inflammatory properties on the endothelial level. Basic science, observational studies and clinical trials have demonstrated that higher tissue levels of omega 3 fatty acids are associated with longer health span and lifespan. This understanding must be balanced with a probable increased risk of AF in certain clinical situations associated with high dose omega-3 supplements as described above (people with known CAD, high risk for CAD, or following and MI). Note that current AHA and ACC dietary guidelines include at least 2 servings of fatty fish per week, one serving provides approximately 1800 mg of omega-3.
Getting omega-3 fatty acids from cold water fatty fish would be ideal. Unfortunately, many individuals do not like salmon, sardines, mackerel or herring and simply will not consume enough of this fish to achieve protective tissue levels. Other species of fish and seafood provide much less amounts of omega 3. Another consideration is that individuals process omega 3 fats differently so different amounts of omega 3 will be necessary to reach the same protective levels in tissue. You can obtain a red blood cell omega-3 index using a home kit and a finger prick without a prescription (https://omegaquant.com/). The sample is mailed in to the lab and results reported directly to you. I have no financial relationship with these folks.
Bill Harris, PhD, is widely published in the area of omega-3 science. He developed the first clinically useful tissue assay which measures the % of omega 3 fat in red blood cell membranes, the “omega-3 index” which is the gold standard for omega 3 research and clinical testing. Although serum levels correlate with the red blood cell index, the later reveals dietary consequences of a 2-3 month period while serum levels reflect just a few days of most recent dietary habits. The red blood cell omega 3 index is analogous to the hemoglobin A1c which reveals average blood sugars over a 2–3-month period. Bill Harris suggests that 1800 mg per day of omega 3 fat consumption (food plus supplements) will achieve an index of >= 8% in most individuals.
Here are some references.
Harris WS, Tintle NL et.al., Fatty Acids and Outcomes Research Consortium (FORCE). Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nat Communications. 2021 Apr 22;12(1):2329. doi: 10.1038/s41467-021-22370-2. PMID: 33888689; PMCID: PMC8062567. https://pubmed.ncbi.nlm.nih.gov/33888689/
“Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids).Similar relationships were seen for death from cardiovascular disease, cancer and other causes”
Blood Levels of Long-Chain n–3 Fatty Acids and the Risk of Sudden Death Authors: Christine M. Albert, M.D., M.P.H., Hannia Campos, Ph.D., Meir J. Stampfer, M.D., Dr.P.H., Paul M. Ridker, M.D., M.P.H., JoAnn E. Manson, M.D., Dr.P.H., Walter C. Willett, M.D., Dr.P.H., and Jing Ma, M.D., Ph.D.
We conducted a prospective, nested case–control analysis among apparently healthy men who were followed for up to 17 years in the Physicians’ Health Study. The fatty-acid composition of previously collected blood was analyzed by gas–liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status.
RESULTS
Base-line blood levels of long-chain n–3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n–3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71).
CONCLUSIONS
The n–3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease.
Heydari B, Abdullah S, Pottala JV, Shah R, Abbasi S, Mandry D, Francis SA, Lumish H, Ghoshhajra BB, Hoffmann U, Appelbaum E, Feng JH, Blankstein R, Steigner M, McConnell JP, Harris W, Antman EM, Jerosch-Herold M, Kwong RY. Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial. Circulation. 2016 Aug 2;134(5):378-91. doi: 10.1161/CIRCULATIONAHA.115.019949. PMID: 27482002; PMCID: PMC4973577. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.115.019949
Conclusions: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care.
Effect of Different Antilipidemic Agents and Diets on Mortality A Systematic Review
Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of Different Antilipidemic Agents and Diets on Mortality: A Systematic Review. Arch Intern Med. 2005;165(7):725–730. doi:10.1001/archinte.165.7.725
Compared with control groups, risk ratios for cardiac mortality indicated benefit from statins (0.78; 95% CI, 0.72-0.84), resins (0.70; 95% CI, 0.50-0.99) and n-3 fatty acids (0.68; 95% CI, 0.52-0.90).
Feuchtner G, Langer C, Barbieri F, Beyer C, Dichtl W, Friedrich G, Schgoer W, Widmann G, Plank F. The effect of omega-3 fatty acids on coronary atherosclerosis quantified by coronary computed tomography angiography. Clin Nutr. 2021 Mar;40(3):1123-1129. doi: 10.1016/j.clnu.2020.07.016. Epub 2020 Jul 22. PMID: 32778459. https://pubmed.ncbi.nlm.nih.gov/32778459/
Conclusions: Omega-3-PUFA supplementation is associated with less coronary atherosclerotic “high-risk” plaque (lipid-rich) and lower total non-calcified plaque burden independent on cardiovascular risk factors. Our study supports direct anti-atherogenic effects of Omega-3-PUFA.
Conclusions: EPA and DHA added to statins prevented coronary plaque progression in nondiabetic subjects with mean LDL-C <80 mg/dL, when an omega-3 index ≥4% was achieved. Low omega-3 index <3.43% identified nondiabetic subjects at risk of coronary plaque progression despite statin therapy
Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006).
Conclusions: In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF (atrial fibrillation). These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.
An omega-3 index of less than 4% is associated with increased CHD risk, particularly for sudden cardiac death. In contrast, an omega-3 index of more than 8% is associated with low CHD risk, whereas the range between 4% and 8% is considered intermediate risk
Risk of sudden death
Alfaddagh A, Elajami TK, Ashfaque H, Saleh M, Bistrian BR, Welty FK. Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients with Coronary Artery Disease: A Randomized Clinical Trial. J Am Heart Assoc. 2017; 6: e006981. 10.1161/JAHA.117.006981. https://pubmed.ncbi.nlm.nih.gov/29246960/
“High-dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well-controlled low-density lipoprotein cholesterol levels.”
Huh JH, Jo SH. Omega-3 fatty acids and atrial fibrillation. Korean J Intern Med. 2023 May;38(3):282-289. doi: 10.3904/kjim.2022.266. Epub 2022 Dec 14. PMID: 36514212; PMCID: PMC10175873 https://pubmed.ncbi.nlm.nih.gov/36514212/
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Effects of omega-3 fatty acid supplementation on the risk of atrial fibrillation. HR, hazard ratio; CI, confidence interval; VITAL, Vitamin D and Omega-3 Trial; ASCEND, A Study of Cardiovascular Events in Diabetes; STRENGTH, Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia; RP, Risk and Prevention Study; REDUCE-IT, Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial; GISSI-HF, Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure; OMEMI, Omega-3 Fatty Acids in Elderly With Myocardial Infarction. Effects of omega-3 fatty acid supplementation on the risk of atrial fibrillation. HR, hazard ratio; CI, confidence interval; VITAL, Vitamin D and Omega-3 Trial; ASCEND, A Study of Cardiovascular Events in Diabetes; STRENGTH, Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia; RP, Risk and Prevention Study; REDUCE-IT, Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial; GISSI-HF, Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure; OMEMI, Omega-3 Fatty Acids in Elderly With Myocardial Infarction. Effects of omega-3 fatty acid supplementation on the risk of atrial fibrillation. HR, hazard ratio; CI, confidence interval; VITAL, Vitamin D and Omega-3 Trial; ASCEND, A Study of Cardiovascular Events in Diabetes; STRENGTH, Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia; RP, Risk and Prevention Study; REDUCE-IT, Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial; GISSI-HF, Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure; OMEMI, Omega-3 Fatty Acids in Elderly With Myocardial Infarction
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
Sorry for the confusion. The website for the International Evolutionary Health Conference changed when the venue changed from Boston to Virtual. Here is the correct website link which gives a list of speakers/topics and sign up information.
Winter approaches with a perfect storm of 3 respiratory viruses, increased indoor activity, dry spaces, and holiday gatherings. The 3 viruses already filling many hospitals (including children’s hospitals) include RSV (Respiratory Syncytial Virus), Influenza, and SARS-CoV-2.
Respiratory viruses spread by aerosol typically enter through the nose and throat. Dry nasal and oral-pharyngeal mucosa (the lining of the nose and throat) presents an ideal incubator for respiratory viruses. With winter comes drier indoor environments created by heating systems.
Indoor conditions, particularly indoor RH (relative humidity) modulate the spread and severity of COVID-19 outbreaks.
The sweet spot was between 40% and 60% humidity to minimize spread and severity of infection.
Here is a picture of the temperature and humidity monitor in my home office.
Note that while outdoor humidity is 55%, indoor humidity is only 34%, short of the “ideal” range for decreased viral transmission and severity. We have a humidifier in our bedroom where the RH is higher.
In addition to a bedroom humidifier we have several HEPA filters dispersed throughout the house. HEPA filters can decrease aerosol (viral load) by 80% or more as can the homemade Corsi-Rosenthal box. HEPA filters and the Corsi-Rosenthal Box also significantly reduce indoor air pollution, potentially protecting us from not only respiratory disease but also heart attacks, strokes, dementia and cancer.
As the winter approaches consider protecting your family and friends from RSV, Influenza, and COVID-19 by utilizing a humidifier and free standing HEPA filters. Improving indoor air quality will have many health benefits.
In the context of the COVID 19 pandemic I will close with the usual summary.
Exercise, especially out of doors in a green space, supports the immune system
Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
Drink water filtered through a high quality system that eliminates most environmental toxins. (Such as a Berkey or reverse osmosis filter)
HEPA filters or the home-made version (Corsi-Rosenthal box) used in your home or workplace can reduce circulating viral load by 80%. This works for any respiratory virus transmitted by aerosol and this winter we have the triple threat of RSV, Influenza, and SARS-CoV-2. It also decreases indoor air pollution.
If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors (Diabetes, pre-diabetes, insulin resistance, hypertension, obesity, heart disease, COPD, asthma, cancer treatment, immune suppression) suggests benefit from a booster. Risk for complications of boosters in adolescents, especially males, without risk factors, may equal benefit. Previous infection with Covid can be considered as protective as a booster. Discuss risk vs benefits with your doctor.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
SARS CoV-2 virus is spread by aerosols. These aerosols contain many viruses carried in a tiny amount of liquid from a person’s mouth and nose as they breath, talk, sing, or yell. Yelling, singing, coughing, sneezing produce more aerosol than breathing. Risk of transmission in a room depends on duration of exposure (time in the room), amount of ventilation, # of individuals carrying the virus present and their activity . A 5 micron aerosol can stay suspended in air for 30 minutes indoors.
HEPA filters (High Efficiency Powered Air-filters) can dramatically reduce the number of aerosols in a room. This includes not only virus carrying aerosols but also small particulate pollutants, both of which impact the health and safety of children and adults in classrooms, meeting rooms and businesses.
HEPA filters range in price from $150 to $800 or more depending on quality, efficiency and how quiet they run. They have been tested in classrooms and hospitals.
In the hospital setting they have dramatically decreased COVID Virus.
To determine how the filters stand up to real-world conditions, Navapurkar and his co-authors installed them in two fully occupied COVID-19 wards — a general ward and an ICU. The team chose high-efficiency particulate air (HEPA) filters, which blow air through a fine mesh that catches extremely small particles. The researchers collected air samples from the wards during a week when the air filters were switched on and two weeks when they were turned off.
In the general ward, the team found SARS-CoV-2 particles in the air when the filter was off but not when it was on. Surprisingly, the team didn’t find many viral particles in the air of the ICU ward, even when the filter there was off. The authors suggest several possible reasons for this, including slower viral replication at later stages of the disease3. As a result, the team says that measures to remove the virus from the air might be more important in general wards than in ICUs.
An Engineering professor and Dean at UC Davis, Richard Corsi, tweeted the design of an inexpensive homemade air filter providing the equivalent aerosol clearing capacity as an expensive manufactured HEPA filter. A colleague in Texas built one with simple components from a hardware store. The result was called the Corsi-Rosenthal box.
Made with four MERV 13 Airfilters, a box fan , duct tape and cardboard.
Dr. Corsi is an expert in the engineering of HVAC systems. He has researched methods to improve indoor air quality and published many scientific studies involving the interaction between pollutants and indoor materials. He estimates that the cost of a home-made Corsi-Rosenthal box is $4.50 per year per student to build and run based on average class size in the US. These are easily made with simple components and instructions available on-line. In fact if you search YouTube you will find many short videos on how to build these in 20 minutes. Their construction and use could easily be a classroom activity.
Here is a picture of the Corsi-Rosenthal box from Wikipedia:
One box can help to improve the air quality in an average size classroom, offering the equivalent of 7 to 8 air changes an hour.
These boxes would not only benefit health by decreasing circulating virus containing aerosols but also filtering out indoor pollutants that come from latex paint, carpet fibers, cleaning chemicals, air fresheners, fire retardants on furniture and clothing, which all release volatile organic compounds (VOCs) that cause lung damage, increase risk of asthma and autoimmune disease. So why have these not been widely used in our schools, homes, and businesses?
Why has the CDC not recommended this simple and inexpensive highly effective risk reduction approach? If widely implemented soon after Drs. Corsi and Rosenthal invented and advocated it’s use, it would have prevented many infections and allayed some of the fear and anxiety of teachers, students and parents. As the flu season approaches, and with the added risk of a triple threat presented by RSV, Influenza, and Covid, all transmitted by aerosol, now would be a great time to build some for your home, business, office or your chidren’s school classrooms.
In the context of the COVID 19 pandemic I will close with the usual summary.
Exercise, especially out of doors in a green space, supports the immune system
Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
Drink water filtered through a high quality system that eliminates most environmental toxins.
If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors (Diabetes, pre-diabetes, insulin resistance, hypertension, obesity, heart disease, COPD, asthma, cancer treatment, immune suppression) suggests benefit from a booster. Risk for complications of boosters in adolescents, especially males, without risk factors, may equal benefit. Previous infection with Covid can be considered as protective as a booster. Discuss risk vs benefits with your doctor.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
An excellent article recently published in the Atlantic was so well written that I have cut and pasted important snippets to help create this post. The review confirms many findings uncovered in my reading of several scientific publications.
20 to 30 percent of patients report brain fog three months after their initial infection, as do 65to85 percent of the long-haulers who stay sick for much longer.
Of long COVID’s many possible symptoms, brain fog “is by far one of the most disabling and destructive,”
It is more profound than the clouded thinking that accompanies hangovers, stress, or fatigue.
It is almost always a disorder of “executive function”—the set of mental abilities that includes:
focusing attention,
holding information in mind, and
blocking out distractions.
Patients state they often lose focus mid-sentence.
Difficulty with simple tasks impairs activities of daily living.
“I couldn’t unload a dishwasher, because identifying an object, remembering where it should go, and putting it there was too complicated.”
The memories are there, but with impaired executive function, the brain neither chooses the important things to store nor retrieves that information efficiently.
Most people with brain fog are not so severely affected, and gradually improve with time. But even when people recover enough to work, they can struggle with minds that are less nimble than before.
“I’ve had surgeons who can’t go back to surgery, because they need their executive function,” Monica Verduzco-Gutierrez, a rehabilitation specialist at UT Health San Antonio.
That specific constellation of problems also befalls many people living with HIV, epileptics after seizures, cancer patients experiencing so-called chemo brain, and people with several complex chronic illnesses such as fibromyalgia.
People with brain fog also excel at hiding it: to protect their jobs when still able to work, or to protect their reputation, or out of embarrassment.
“I know my value in many people’s eyes will be diminished by knowing that I have these cognitive challenges.”
Individuals with previously above average cognitive ability often test “normal” but suffer significant loss compared to their prior ability.
A team of British researchers analyzed data from the UK Biobank study. The findings revealed structural changes in the brain with loss of tissue on MRI scans that correlates with symptoms.
They found that even mild infections can slightly shrink the brain and reduce the thickness of its neuron-rich gray matter. At their worst, these changes were comparable to a decade of aging.
They were especially pronounced in areas such as the parahippocampal gyrus, which is important for encoding and retrieving memories, and the orbitofrontal cortex, which is important for executive function.
In most cases the virus probably harms the brain without directly infecting it.
Inflammatory chemicals can travel from the lungs to the brain, where they disrupt cells called microglia (immune cells in the brain).
In their presence, the hippocampus—a region crucial for memory—produces fewer fresh neurons, while many existing neurons lose their insulating coats (demyelination), so electric signals now course along these cells more slowly.
These are the same changes seen in cancer patients with “chemo fog”.
Neuro-inflammation is “probably the most common way” that COVID results in brain fog, but that there are likely many such routes, such as reactivation of dormant viruses such as Epstein-Barr virus, which has been linked to conditions including ME/CFS and multiple sclerosis.
These problems can be exacerbated or mitigated by factors such as sleep and rest, which explains why many people with brain fog have good days and bad days.
Although other respiratory viruses can wreak inflammatory havoc on the brain, SARS-CoV-2 does so more potentlythan influenza.
For adults following SARS CoV-2 infection:
risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period.
For children following SARS CoV-2 infection:
in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 [95% CI 0·94–1·10) or anxiety (1·00 [0·94–1·06]) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 [1·09–1·33] to 2·16 [1·46–3·19])…. Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days).
The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects.
There are no proven drug treatments for long-haulers.
But there is hope.
Cancer researchers have developed drugs that can calm inflamed microglia in mice and restore their cognitive abilities;
“Metformin can promote the regeneration of neural precursor cell populations and improve cognitive function in a preclinical model of cranial radiation and a pilot clinical study of children after cranial radiation and chemotherapy.”
With regard to long-haulers, better sleep, healthy eating, and other generic lifestyle changes can make the condition more tolerable. Breathing and relaxation techniques can help people through bad flare-ups; speech therapy can help those with problems finding words.
“Some people spontaneously recover back to baseline,”
The largest group of long-haulers—those whose brain fog has improved but not vanished, can “maintain a relatively normal life, but only after making serious accommodations,”
Patients struggle to make peace with how much they’ve changed and the stigma associated with it, regardless of where they end up.
People with ME/CFS learned this lesson the hard way, and fought hard to get exercise therapy, once commonly prescribed for the condition, to be removed from official guidance in the U.S. and U.K.
In summary:
Brain fog can occur even after mild or asymptomatic Covid-19.
Although many patients improve over time, many are left with disability that can range from mild to incapacitating.
Although these symptoms can occur following any viral infection, SARS CoV-2 seems to produce this with greater frequency compared to other viruses.
Chronic brain inflammation is the likely cause in many individuals.
Reactivation of Epstein Barr and/or other dormant viruses is suggested by various immune markers.
The immune signature also suggests an immune response that mimics persistent infection in the absence of live SARS CoV-2 virus.
Post exertional malaise following physical or mental exercise is a common and debilitating symptom without proven treatments. However there are guidelines that may help mitigate this devastating condition.
Exercise, especially out of doors in a green space, supports the immune system
Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
Drink water filtered through a high quality system that eliminates most environmental toxins.
If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors means clear benefit from a booster.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
My friend Diana Rogers, started the Global Food Justice Alliance. This organization brings unbiased science to the discussion of meat consumption as it relates to health AND the environment. As discussed previously (see regenerative agriculture posts), properly raised ruminants (beef, pork, lamb, etc.) are ecologically sound, help create soil and fight climate change, and provide important nutrient dense food for people of all ages. The anti-meat narrative in popular media presents a false and dangerous position that threatens our environment, soil conversation/creation, and health.
Regenerative sustainable agriculture (depicted on the right) , minimizes use of fossil fuel and fossil oil based fertilizer. Instead it utilizes ruminant animal waste for fertilizer, creates living soil and biologic diversity. Mono-agriculture depicted on the left, destroys soil, depletes nutrients in food, contaminates our food with pesticides, creates downstream runoff environmental degradation, and contributes to climate change. The documentary “Kiss the Ground” documents these important concerns.
In the context of the COVID 19 pandemic I will close with the usual summary.
Exercise, especially out of doors in a green space, supports the immune system
Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
Drink water filtered through a high quality system that eliminates most environmental toxins.
If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors means clear benefit from a booster.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
I recently gave a talk at the AHS 2022 meeting held at UCLA. You can view the video here:
This first slide gives a good overview.
The presentation covers a quick review of my presentations given last year at the PAH 2021 annual meeting (virtual) with additional information on long Covid.
Multiple nutrients acting synergistically support a balanced response to viral infections, including SARS CoV-2. Here is a picture.
The take home message is that no single nutritional intervention is likely to have significant impact with an acute infection unless all but one nutritional component is optimal. Nevertheless, there is compelling evidence that Vitamin D deficiency is rampant in the developed world and if one nutritional intervention is likely to be of benefit, Vitamin D supplementation, particularly in high risk populations, presents the most likely candidate. As usual, preventive supplementation would be preferable to rescue high dose intervention.
In a study of frail elderly hospitalized patients, regular vitamin D supplementation was associated with decreased mortality as demonstrated here. Compared to no supplementation, regular supplementation was associated with a 93% reduction in risk of death.
A study from Spain with very high dose Vitamin D in the form of Calcifediol showed significant benefit in hospitalized patients, suggesting that Vitamin D deficiency was prevalent in that population and that such a treatment intervention should be widely considered.
Calcifediol Treatment and COVID-19-Related Outcomes
The following graphic from another nutrition review article, with red additions added by myself, demonstrates the complex interaction between nutrition and the two main components of our immune system, innate immunity (immediate response) and adaptive immunity (based on immune memory). Again red highlights added by yours truely.
And here is a slide from my lecture with quotes from that article.
Yet most Americans are deficient in many of these essential nutrients as depicted here. The percentages represent the % of Americans that fall below the estimated amount required to prevent deficiency in HALF of adults (a very low standard).
The EAR is a very low bar to meet, yet many Americans fall below even that low standard.
The SARS CoV2 virus interferes with a crucial component of the the initial (innate) immune response, the production of interferon 1 and the signaling of interferon one to immune cell mediators as depicted in this graphic.
SARS CoV2 on the left is compared to Virus X on the right. On the left interferon 1 (IFN) production and signaling is blocked by the virus, interfering with an effective and controlled immune response, on the right IFN is not blocked. A cascade of events results in TOO LITTLE, TOO LATE, AND THEN TOO MUCH of an immune response, producing a cytokine storm.
Obesity, insulin and leptin resistance, also interfere with the production and signaling of interferon. The result is that people with insulin and leptin resistance (pre-diabetes, Type 2 Diabetes as well as sarcopenia) experience a double hit. First the virus itself disrupts the immune response and superimposed upon the viral effect is the effect of insulin and leptin resistance on the immune response.
SOCS: suppressor of cytokine signaling. Several recent viral studies have shown that viral genes can hijack SOCS1 to inhibit host antiviral pathways, as a strategy to evade host immunityOn the left Interferon production and signaling are normal and a successful immune response is mounted. On the right the presence of insulin and leptin resistance, associated with obesity results in an initial inadequate response and a late excessive response. TOO LITTLE, TOO LATE, THEN TOO MUCH.
Factors that can quickly impact insulin and leptin resistance include all the components of an ancestral lifestyle depicted in my website graphic. A paleolithic or ancestral diet that eliminates sugar added foods and beverages, replacing those empty calories with nutrient dense foods, exercise, adequate restorative sleep, stress reduction, avoidance of environmental toxins, social connection. All of these affect health in general, mitigate insulin and leptin resistance, and support a balanced immune response to viral infection. The circle of health depicted below is surrounded by the many deleterious aspects of modern living. Thus, a mismatch between our evolutionary biology and present day life.
Here is a slide from my lecture that lists many lifestyle factors that can impact infection with any virus, including SARS CoV-2
My lecture also included discussion of Long COVID, theories of etiology and pathophysiology which will be discussed in my next post.
For the full lecture which is about 34 minutes long, please follow the link above.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
Again, another biased article claims to demonstrate the dangers of red meat. There are so many problems with the author’s analysis and conclusions it is hard to know where to begin. Rather than go through the nitty gritty here, just head on over to this analysis to read another debunking of the same litany of bad science.
Exercise, especially out of doors in a green space, supports the immune system
Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml. (read this Open Letter)
Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs.
THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.
Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.
Practical Evolutionary Health 