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“A phenomenon called “original antigenic sin” (OAS) was firstly proposed by Francis 6 in 1960. This phenomenon occurs in the second exposure of the immune system to a similar pathogen to which it has previously been exposed. In this situation, the immune system progresses to the memory response, generating cross-reactive antibodies that may not be effective against the new pathogen. 7 In addition, it has been speculated that overproduction of memory B cells could compromise the activation of naïve B cells capable of producing efficient and novel antibodies. 8 In this way, OAS can trigger immune evasion of the emerging variants in those who had been affected by or vaccinated against former versions of the pathogen. In the context of coronaviruses, cross-neutralization is a rare event, but cross-reactivity in antibody binding to spike protein is common in SARS-CoV-2 and SARS-CoV. 9 Furthermore, some degrees of cross-reactivity have also been demonstrated between seasonal coronaviruses and SARS-CoV-2. 10 Aydillo et al 11 reported a strong back-boosting of antibodies in SARS-CoV-2–infected patients previously infected with human β-coronaviruses. Interestingly, a negative correlation was observed between pre-exposure to human β-coronaviruses and induction of antibodies against SARS-CoV-2, mentioning the reduction of de novo humoral immune response and occurrence of OAS in patients with pre-existing immunity against related coronaviruses. 11
The impact of OAS in developing vaccines is of paramount interest. The hypothesis of antigenic distance was proposed to explain how the efficacy of vaccines could be influenced by the difference or relatedness of prior vaccinations. This hypothesis is substantially evident in the case of dengue fever-related vaccine research. Once an individual is immunized against a dengue virus variant, the booster shot for the second variant is unlikely to be successful because it triggers only the original neutralizing antibodies rather than effective antibodies for the new variant. 12”
1. A2 Milk for Kids [20:08]
Nate says:
Hi Robb, my wife is wondering if A2 would be better for our son than nut milks. I couldn’t find anything on your site about A2 milk, but searching online have found that it lacks A1.
We give our kid nut milks for calcium, but have been reading that nut milks are estrogenic, so are looking for other calcium sources.
I read the paleo solution 12 years ago and know how you treated dairy in the book. My gut feeling is that A2 milk is from cows where A1 has been bread out, but it is still dairy and should be avoided.
Any thoughts on A2 milk and if it is better than regular dairy?
Thank you.
-Nate
Milk proteins and human health: A1/A2 milk hypothesis
2. Lean Mass Hyper Responder with Type 1 Diabetes [22:59]
Alex says:
Hi Robb,
Thanks for your podcast with Bill Cromwell and specifically for the deep dive into LMHR. Actually I wish the dive was even deeper, hence the discussion and questions below 
I am a 50 year old male. Have been following low carb (progressively from low carb to mostly keto to mostly red meat with occasional vegetables and berries) for the last 6 years. I developed Type 1 Diabetes when I was 33 after 13 years on SAD and 20 years on the Soviet Union diet (whatever that was). I am pretty active: kettlebells a couple of times a week, tennis a couple of times a week and soccer a couple of times a week.
To play back on your frequently asked question: “How do you look, how do you feel, how do you perform?”:
– I look great (5’ 11’’, 165 lbs), very lean, toned muscles
– I feel great
– I play soccer with a number of 20 year olds and I’m able to outlast many of them in terms of my energy and fitness. I didn’t get into sports until my late 20s.
What I’m describing is not different at all from other LMHRs who seem to be actually feeling and performing even better. Ok, fine — looking better too!
So clearly LMHR is a phenotype, which on the surface seems to be selecting for great health and athletic performance at the expense of our ability to survive during ice age, since we can’t store enough fat to save our lives! At the same time, we all have high LDL — a dubious metric that the Pharma industry is obsessed over because of the correlation it has with the health of a completely different phenotype. Is it even desirable for LMHRs to have a low LDL?
Now, this doesn’t mean that I don’t take you, Bill Cromwell or Peter Attia seriously. I do and, hence, I’m concerned. So is there another evolutionary trade-off? Is the payoff for our excellent health and performance is that we will all die early from the heart disease?
Assuming that high LDL is definitely bad for us, what sort of changes in lifestyle, nutrition or medication would you recommend? For me personally (keep in mind that I have T1D), my average HbA1c went from 6.7 to low 5.7 and my average LDL went from 149 to 361 after switching to low carb. Is it possible to achieve both low A1c and LDL?
Thanks again for all your and Nicki’s work!
-Alex
3. Fucoxantin and CLA for Fat Loss? [32:02]
Christina say:
Hi Robb and Nikki! I’ve been a fan and have followed since 2011. Started my health journey with your book, Rob, Paleo Solutions! It changed my life forever! Now I’m a science nerd.. lol.
Anyway, what are your thoughts on CLA supplements used for inhibiting fat storage and also for helping to rid the fat in the cells? It seems to be a craze with certain companies selling it with a ton of testimonials that this stuff really works. I’m very skeptical.
Also, how about Fucoxanthin? Does it help with brown fat creation within the body?
How beneficial are these 2 types of supplements when it comes to aiding your body in fat loss?
Thanks so much for all you do… I would not be where I am TODAY, without you!
Fucoxantin: a treasure from the sea
4. Bile reflux, Gallbladder, Woe [40:16]
Phoenix says:
Dear Robb and Nicki,
I’ve been a listener and reader ever since holy cats days in college, 10 years ago. Three years ago I needed gallbladder surgery. I had very few side effects, as I eat pretty healthy. But, I was also struggling with alcohol and in a difficult relationship. Both got the boot around seven months ago, but due to personal stuff with the breakup, I was under a huge amount of stress. Suddenly, I had bile reflux. It’s a frigging nightmare. I now take sucralfate and a bile binder but they are horrible to time well because I need a small snack when I wake up or else I’m queasy. Red meat and pork often set me off with heartburn. I used to eat tons of veggies but too many of those hurt my stomach now. I know I need more protein. It feels like one extra bite is the difference between puking at 3am and being ok. I’m 5’5″ and an out-of-shape 150 lbs. I feel like a tick, with a chonky belly and skinny limbs. I just had bloodwork done and my white cell count and platelets are low (2.4 and 50). My cholesterol is on the higher side, but my glucose and A1C are normal.
I don’t know what to do. Plus, my emotional trigger for sobering up was my ex’s drunken behavior. No more ex, and I’m trying to find healthy outlets for my ADD/depression-tending mind so I don’t hit the bottle. Are there any recommendations you might have for physically rebuilding?
Thank you, from a longtime fan,
Phoenix
5. Post-Diverticulitis Recovery Diet [48:05]
Sarah says:
Hi Robb & Nicki,
My husband ended up in hospital last June with what eventually turned out to be diverticulitis. This came completely out of the blue as he’d always had a pretty stellar gut beforehand. After he was discharged he did not have the recovery we expected and eventually ended up on a second round of antibiotics and a liquid diet again.
The standard recommendation after diverticulitis is to gradually increase fibre content and a diet low in fibre is cited as the cause of it. This was definitely not the case for my husband as he was eating a lot of fibre before his hospital admission. After some dietary experiments, we have since realised that he can now only tolerate a very small amount of it or he ends up in pain. His current diet consists of white rice for carbs, traditional home-cooked dishes minus the vegetables (he’s from South-East Asia), plus beef and fish. Unfortunately, he still hasn’t managed to regain all of the weight and muscle that he lost. For some context, he’s in his early 40s, about 5’10” and weighs about 143 lbs. He’s very active, works out regularly and has a decent amount of muscle on his upper body.
Do you have any recommendations on the most suitable diet for him to follow (he also can’t tolerate dairy) and is there anything he should definitely avoid? He’s tried some weight gain powders recently but they seem to cause him pain as does some forms of physical exercise and movement. Is there any way that he can fully recover from this?
Many thanks,
Sarah
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