some mechanisms and effects of nutritional ketosis

Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration (Li et al., 2019)

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New review out, that got a lot of stuff right!

For example, it’s useful to talk about starchy/net carbs in terms of % of calories because for people with vastly differing total daily energy intake, the actual grams will differ considerably. Also, if you want to know if your diet is ketogenic, there’s a neat little trick.

Topics covered: biochemistry of ketogenic diet-mediated energy generation, general health, type 2 diabetes, weight loss, fatty liver, neurodegeneration, muscle biology, and more!

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quantum biology – it’s real

First things first: new drug on the market. You know how anti-histamines (eg, diphenhydramine) are sedative? Histamine in the brain is ‘alerting’ – in the gut it’s involved in gastric secretions and in the immune system it makes you itchy.

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There’s a new anti-anti-histamine that appears to be effective for treating excessive daytime sleepiness in people with narcolepsy. Pitolisant.

Pitolisant is apparently highly selective for the brain H3 histamine receptor so it doesn’t mess with your guy or make you all itchy.

No biohacks here, just learned about this compound and thought it was a cool concept and may be very helpful for some people.

I’ve been watching lectures by Sean Carroll and Philip Ball lately. If you have any interest in physics, highly recommended! Quantum biology…

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Insulin Hypersecretion

The relationship between hyperinsulinemia and insulin resistance is a bit murky (Nolan and Prentki, 2019). Dr Corkey gave a good presentation on this, which Tl;dr: goes something like this — stuff in the environment, your food, etc., causes insulin hypersecretion. Not regular carb-induced insulin secretion, and not enough to cause hypoglycemia… just enough to cause insulin resistance.

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I also recommend checking out some of Brownlee’s work on the microvascular and macrovascular consequences of hyperglycemia — it seems complementary to this (eg, Giacco and Brownlee, 2010; Shah and Brownlee, 2016). A lot has changed in the last decade, but there are still a lot of relevant points, or at least things to be aware of.

The Nolan and Prentki review is good – the basis is that there is no grand unifying theory underlying metabolic syndrome agreed upon by clinicians and scientists. I concur. Also, there probably isn’t one single mechanism because there are many different phenotypes/manifestations.

Definition: when I say beta cell failure in the context of T2D, I don’t mean dead failing beta cells, I mean beta cells that are trucking out more insulin than ever… but it’s not enough to keep glucose under control (due to insulin resistance). Now that that’s out of the way…

For the rest of this article and more, head over to Patreon! Five bucks a month for access to this and all previous articles. It’s ad-free and you can cancel if it sucks 

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#eTRF OMAD (Singh et al., 2019)

I’m not a huge fan of OMAD (one-meal-a-day) — if it works for you, cool, but it’s not where I’d start. Harder to meet protein requirements, metabolic mayhem refeeds, disrupted sleep quality, etc. But it helps some people control calorie intake (I understand, it can be difficult to overeat all of your daily calories in one sitting… very full belly!)

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Franz Halberg, one of the fathers of chronobiology, did some pioneering studies on AM/PM meal timing.

He and his contemporaries and students (eg, Jacobs & Hirsch) were among the first to study OMAD breakfast vs. dinner.

Tl;dr: they took a group of people and gave them all of their food in one sitting – breakfast or dinner. The breakfast group lost weight. Upon reviewing the diets, it turns out the breakfast group was eating less. So they followed-up…

can you guess what happened?

For the rest of this article and more, head over to Patreon! Five bucks a month for access to this and all previous articles. It’s ad-free and you can cancel if it sucks 

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Circadian rhythms – exercise & meal timing

Two studies on exercise and a review on meal timing.

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Single-session exercise studies show better performance in the afternoon, although this is trainable – consistent AM training improves performance in the AM and PM whereas consistent PM training does not improve AM performance.

Chronotype effects? Circadian rhythms?

But that’s neither here nor there. Exercise is better than no exercise, and if you have the luxury to choose, evidence favors AM.

Comparison between the effect of 6 weeks of morning or evening aerobic exercise on appetite and anthropometric indices: a randomized controlled trial (Alizadeh et al., 2017).

Good study – main outcomes were body weight, appetite, and ad lib food intake.

Exercise doesn’t burn a whole lot of calories but it’s very good for you. A goal of this study was to see if exercise timing influenced appetite and ad lib food intake, which have a greater role in regulating body composition.

The exercise intervention was modest, ~30 minutes of cardio in the morning or afternoon. Main findings: significantly greater reduction in body weight, BMI, waist circumference, abdominal circumference, and abdominal skin fold thickness in the morning exercise group.

The morning group also spontaneously ate less throughout the day despite no difference in appetite/hunger scores or exercise intensity between the groups. Boom.

Does AM exercise and skewing kcals earlier in the day work for you? Will you try it?

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A non-zealot keto study!

These researchers were too interested in their sophisticated instruments for assessing body composition than to care about keto per se. Lol (Buechert et al., 2019)

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Small study (n=12), duration was 6 weeks.

Keto diet was good and well-adhered to. Urinary ketones positive on 97% of the days. The “rules” were also good, simple: no processed foods, be aware of hidden carbs in stuff like gum, lunch meat, etc. Fruits and vege were fine as long as they were within the carb limits and we know that they were, because positive urinary ketones. They were allowed nuts and dark chocolate, too.

It wasn’t supposed to be a weight loss study, but they all lost weight.

Weakness: no control group – only before/after comparisons.

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New low carb + IF study with weird results

Alternate day fasting combined with a low-carbohydrate diet for weight loss, weight maintenance, and metabolic risk reduction (Kalam, Varaday et al., 2019)

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Study design: 1 day of 600 kcal protein shakes then 1 day of protein shakes and normal ad lib food intake. “Alternate day fasting (ADF).”

There was some bias in the text/discussion (in favor of ADF; blamed low carb), but credit where it’s due – one of the more sensible lines in the paper: “It is also likely that only a selected group of individuals with obesity may find this diet tolerable and suitable for their lifestyles.”

Intermittent fastin concept – empty plate on blue background, copy space

With that, I agree. LC/ADF isn’t where I’d start, but it could work for some. However… it just didn’t seem to do so in this study very well.

Be aware of this -> “Fasting increases risk of binge eating and bulemic pathology: a 5-year prospective study” (Stice et al., 2008)

Tl;dr: the participants lost weight but didn’t improve any primary endpoints – triglycerides, fasting glucose, and insulin resistance didn’t change.

O_o

How do you lose 5 kg of fat and none of it from visceral adipose? ADF?

How do you lose weight with LCHP but not improve any metabolic markers? ADF?

-> a bit of the blame was shifted toward the LC component, although none of that stuff really happens in LC weight loss studies… suggests ADF...

ONE HINT FROM A MOUSE STUDY

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Red Light on the Brain and More

Final installment (probably) on RLT/PBM.

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Cognition

LLLT has shown promise in improving cognition [R].  

In a study testing broad neurocognitive functions, in comparison to placebo, participants who received LLLT showed more positive effects in reaction time, memory, and mood [R].

LLLT improved aging-related and vessel disease-related cognitive decline in an elderly population [R]. Laser treatment also improved memory, attention, and executive function in a population of patients with dementia [R].

Red light therapy has been studied in a wide variety of conditions including, stroke, Alzheimer’s disease, Parkinson’s disease, depression, and cognitive enhancement in healthy subjects [R].

Mental Health

LLLT has also shown promise in traumatic brain injury, with positive effects on sleep, mood, and anxiety [R].  

For example, one case study who underwent 20 treatment sessions over the course of two months experienced decreases in depression, anxiety, headache, and insomnia, while cognition and quality of life improved [R, R]. However, caution is warranted because these findings have yet to be replicated in a large-scale double-blind placebo-controlled randomized clinical trial.

LLLT is still in the experimental phase for emotional conditions, but some studies have shown a positive effect on major depressive disorder, simultaneous anxiety, and suicidal ideation [R].  

In a small study in patients with major depressive disorder and simultaneous anxiety LLLT showed improvements up to two weeks after treatment [R]. This was confirmed in another small clinical trial [R] and a larger one in patients who responded positively to behavioral therapy [R]. 

Anyone using this or interested in trying? Drop a note in the comments!

For more of the studies on PBM, head over to Patreon! Five bucks a month for access to this and all previous articles. It’s ad-free and you can cancel if it sucks 

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Red Light, Green Light, Photobiomodulation

Part 1 HERE

Now on to the [mostly] human studies –

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Low level laser therapy (LLLT), also known as photobiomodulation, is the use of low-energy red, near-infrared, and infrared light to treat a variety of health conditions like pain and inflammation but it can also be used to improve physical performance. 

Introduction

Essentially, a low-powered laser or light-emitting diode (LED) is used to shine a specific wavelength of light onto the skin of a patient to elicit certain physiological effects in the underlying tissue without causing any damage. Some examples of conditions often treated with LLLT include rheumatoid arthritis, chronic neck and back pain, periodontitis, and muscular injuries.  

The light source may be in the form of a laser or LED and the wavelength of light produced usually falls into the range of 660 nm (red) or 800-900 nm (near-IR/IR) [R, R]. 

Treatment sessions are usually short, lasting only seconds to minutes in duration, and are usually conducted every other day for weeks to months.

Surprisingly, unlike many other treatment modalities used to address similar conditions, there are virtually no reported side effects from LLLT.  

Effects of PBM/LLLT

Inflammation 

One study examined post-injury pain and recovery time in athletes who were treated with an average of four 20-minute sessions of infrared light therapy and compared them to historical values [R]. The average recovery time in athletes treated with LLLT was significantly shorter at 9.6 days when compared to the average anticipated recovery time of 19.2 days. 

A review on muscle repair in animal models concluded red light therapy has the capacity to reduce inflammation, positively impact growth factors, and increase angiogenesis [R]. One animal study showed that LLLT reduced inflammation in an injured muscle [R]. 

A well-known effect of chemotherapy is oral mucositis, which is inflammation that results in the  breaking down of the lining of the mouth. A systematic review concluded LLLT significantly reduced the incidence and severity of chemotherapy-induced oral mucositis [R].  

A study on chemotherapy patients showed a significant reduction in self-reported pain with LLLT [R].

 


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 are the bomb. Seriously! And if you like spicy… the former are a little heavier and don’t have a spicy option [yet]

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red light therapy: don’t write it off yet –

I wrote an article about the human studies with red light therapy / photobiomodulation (PBM) a few years ago and didn’t publish it. I’ll update it and follow-up soon. In the meantime…

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Don’t write off the potential of PBM. We accept many biological influences of light – vitamin D synthesis, circadian rhythms, mood disorders, getting a tan and some endorphins, artificial light and blue blockers – and that’s just the stuff most pertinent to humans.

PBM: what’s it supposed to do?

help with wound healing & pain, inflammation & swelling, although it’s actively being studied in many other contexts – notably, to do with spine/nerves/brain stuff

Some people think it’s important to focus on wavelengths 600-700 nm (for superficial applications) and 780-900 nm (for deeper tissues) and not in between because in part, too much total PBM might reduce efficacy so cut out the ones with less biochemical activity so you can get more of the active wavelengths (Chung, Hamblin et al., 2012).

Disclaimer: there are a lot of inconsistencies in the PBM literature. Different doses, duration, surface area exposed, etc., etc., that make it hard to come to firm conclusions on any of it. That, plus, some of the units can get pretty pricy, especially since there’s no clear guarantee they’ll do anything for you. I feel ya.

One effect that seems pretty consistent is on improving skin health/appearance.

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