About This Episode
The world seems to be in a holding pattern, waiting for a new blockbuster vaccine.
The problem with this one-bug, one-drug approach is that viruses mutate, and novel bugs will emerge in the future as they have in the past.
(Needless to say, vaccines have unintended side effects and may not offer lasting protection to those with metabolic disease.)
Scientists, like today’s guest Brianna Stubbs, PhD, are urging us to consider novel approaches, such as dietary strategies that bolster our immune resilience.
Stubbs shares key insights from her recent collaboration with a group of diverse scientists and reviews the details about how we can take action.
Stubbs, B., Koutnik, A., Goldberg, E., Upadhyay, V., Turnbaugh, P., Verdin, E., Newman, J. (2020). Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections Med https://dx.doi.org/10.1016/j.medj.2020.06.008
04:23 Immunometabolism: We can influence our body’s metabolic system to affect our immunological response.
04:56 Our immune response is complicated, such as the balance between immune activation and immune suppression. Different immune cells are activated at different times throughout the immune response and have metabolic states that transition.
07:55 Metabolic inflexibility and poor glycemic control are linked to poor outcomes from COVID. Dr. Stubbs paper addresses the impact of ketones upon the immune system as well as the potential comorbidities from having contracted COVID.
11:40 There is a great deal we do not understand about COVID having to do with metabolism.
13:23 There are many different subtypes of T cells that work in concert.
14:30 Because there is so little known about corona virus, we do not know if the ketone biology that we see in other inflammatory situations would apply.
15:03 Our immune systems know how to deal with a virus, but, with this virus, we are seeing inappropriate immune responses: delayed first response and then a hyperactive immune response, leading to acute respiratory distress syndrome.
16:28 NLRP3 inflammasome is a protein complex that assembles as a result of inflammatory stimuli. It expedites the release of cytokines. BHB ketones, in some animal and invitro studies, have been shown to inhibit the formation of the NLRP3 inflammasome, decreasing the amount of pro-inflammatory cytokines. In human studies, the pro-inflammatory cytokines have increased with elevated ketones.
18:15 NLRP3/BHB/Glucose interaction: In one study, they tritiated up BHB and down glucose to find a sweet spot. At high levels of glucose, BHB did not inhibit NLRP3 inflammasome. The anti-inflammatory effect could be why SGL-2 inhibitors used in the treatment of diabetes decrease cardiovascular disease.
19:50 There are metabolic differences between animals: mice vs rats, different strains of mice, and humans. It is good to remember this when reading study results.
21:46 NLRP3 is downstream from the transcription factors that affect gene expression.
23:39 Great Controlling Nucleotides: every reaction metabolism in our cell uses NAD or NADH. In the cytoplasm in our cells we have NADP and NADPH. It is almost like a redox buffering capacity.
24:00 Too much reductive stress is bad. You cell tries to keep itself in a sweet spot.
24:15 To fight Corona virus you need an oxidative response in your immune cells, because production of radicals to help to kill infected cells and destroy or harm the virus. As your immune response is mounted, the cell can lose some of its buffering capacity, making it more vulnerable to damage.
24:52 Ketone metabolism can boost the ability in the cell’s cytoplasm to be able to absorb some homeostatic challenges. It provides an energy reservoir for our cells to be able to deal with stressful situations.
27:17 The Horvath clock tests your biological ageing. Edifice Health tests ageing via your immune status. Longevity is the next hot topic for research.
30:10 Ketones are protective against LPS and may also be protective against viral inflammation. Systemic inflammation is easier to study and make extrapolations from than inflammatory stress triggered by bacterial threat.
31:10 Being on a ketogenic diet or taking exogenous ketones may help with recovery. The recovery from the virus can be long. The longer they are hospitalized, the harder it will be for them to recover their functionality.
33:10 There is little catabolism In the context of low insulin on a ketogenic diet. It may be that ketone bodies are what keeps the low insulin state from becoming highly catabolic.
35:26 MCT rely upon your body’s ketogenic process. Ketone salts deliver BHB directly into the blood, so there is no hepatic ketogenesis. Ketone esters, depending upon the compound, may include some natural ketogenesis.
36:02 There are molecular signatures to when the liver makes its own ketones.
36:53 Acetoacetate does some things that BHB does not, but it is challenging to measure.
37:32 It is hoped that as we understand disease better, we can target the metabolic countermeasure specifically and improve outcomes.