A few years ago I read about the grapefruit diet. In short you drink grapefruit juice, coffee and eat a couple of eggs - around 3 times a day.
Now this is lacking in fibre and a number of other key nutrients and not a long term solution however I was intrigued about the inclusion of grapefruit. It turns out grapefruit increases insulin sensitivity which is a good thing for controlling weight and also avoiding diabetes.
How does it do that, I wondered? Well, a compound in grapefruit activates something called AMPK. This enzyme also activates insulin sensitivity and a number of other cool things. When we eat less or embark on fasting this pathway is one of the key regulators in making all the cool stuff happen from fasting.
What are the benefits of fasting?
- Fat loss
- Not being tied to the fridge
- Not having to think about snacks and food all day long
- Anti-ageing benefits
- Cognitive benefits, brain regeneration
- Clearing up debris in the blood and body = autophagy
All of these can be enhanced through helping out AMPK – an enzyme which helps all fasting processes. Read on to learn about fasting mimicking foods and supplements.
Fasting reduces calorie intake, blood pressure and increases weight loss without calorie counting.
Fast track time-home messages;
- Eat within a time restricted period
- Eat healthy
- Use high polyphenol foods e.g. eat the rainbow
- Use Aminos to fuel exercise
- Have fun and enjoy the new leaner look
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What is AMPK?
AMPK is an energy sensing enzyme. Specifically, it is released in response to declining and lower levels of ATP in the cells. Its purpose is to help maintain energy homeostasis in the cells. As more energy is burnt, more needs to be released from other areas of the body to replace this.
Key Actions of Interest for Activating AMPK Pathway;
- Increased insulin sensitivity and glucose disposal – lower diabetes risk
- Enhanced Endurance Capacity
- Anti-cancer effects
- Neuro-regenerating effects
- Longevity Benefits
- Enhanced Fat Burning
- Preserves muscle mass
It’s a good things to activate….. best ways are to fast and take loads of phytochemical rich foods, herbs, spices, veggies, berry fruits… there’s a big list at the end of the document….
Foods to increase include these;
Here’s a diagram of some of the pathways which get switched on through activation of the AMPK enzyme;
So if we burn up a lot of energy in the cells and don’t consume much energy we tend to activate this pathway more significantly. As such this enzyme forms part of the fed and fasted states of human metabolism. It’s a survival enzyme. Levels tend to decline with age.
Inflammation blunts AMPK release. Using anti-inflammatory strategies will assist AMPK.
“As energy is used by cells, ATP breaks down into ADP (which has less energy potential); ADP then breaks down into AMP (which has the least energy potential of all three). This is where AMPK comes in – it senses the relative ratios of AMP/ADP/ATP, and tells the body if more ADP is needed so that proper functioning can continue”.
I was reminded about this enzyme a few years ago when looking at the effect naringenin a compound in grapefruit had on influencing glucose uptake into cells. The compounds stimulates glucose uptake through increasing insulin sensitivity in the cell. It does this through stimulating AMPK. This effect maybe independent of lower fuel supply in the cell. It could one of the reasons the grapefruit diet helped fat loss. Compounds such as naringenin are known as fast mimicking compounds dude to their effect on the AMPK enzyme. However useful these compounds are the overriding mechanisms activating AMPK involve energy balance and exercise.
The two most powerful ways to increase AMPK are exercise and controlling energy intake – fasting + exercise appear to be powerful ways to stimulate this enzyme quickly.
AMPK forms part of a seesaw in the energy sensing elements of human metabolism.Generally the bigger players in the fed and fasted pathways will allow for sufficient activation of each part of the cascade. When insulin, stored energy and calories are high, AMPK activation will be lower. When insulin, stored energy and calories are lower AMPK activation will be greater. Opposing factors will tend to, but not always switch off the other factors. E.g. when insulin is higher AMPK should be lower. When mTor is higher AMPK should be lower. One exception to this is mTor stimulated release through key amino acid supplementation when in a fasted state. More on this below;
- By under feeding and over feeding you can active each branch of the anabolic catabolic cascade, thereby enjoying the maximum benefits of each pathway
- Fasting reduces overall energy intake, improves body composition and improves and counteracts most risk factors associated with metabolic syndrome
- Compounds and foods can support fasting and smooth these pathways – allowing for less extremesin calorie depletion and surplus to maximise the health benefits
- AMPK appears relies on and facilitates many of the benefit from fasting
- Fasting and lowered calorie intake reduces systemic production of insulin
- Fasting may have an anti-cancer effect
- Fasting allows for great brain protection and regrowth of neurons
- Increased production and efficiency of mitochondria in the cells
- Exercise and a reduced intake of food with fasting blocks appears to activate AMPK best
- Exercise followed by fasting appears to stimulate fitness adaptations fastest
- As with anything too much fasting and not enough feeding will down regulate metabolism
- Too much fasting and not enough feeding may decrease overall nutrient availability
FED OR FASTED
One of the 1st things you learn in human metabolism is about the fed or fasted state. These states are sometimes referred to as the absorptive and post absorptive states. In the fed state we are ingesting, assimilating and internalising the foods we eat. The main hormone which helps us internalise the external environment is insulin. This is an anabolic state.
Because this state involves ingesting and storing energy it’s less likely the AMPK enzyme will be switched on.
Once we have finished this absorbing phase our bodies shift into post-absorptive. In this phase are body is using all the energy it’s stored and other hormones come into play to create energy. There’s many more hormones to create energy than store it. The main opposing hormone to insulin is glucagon, others will increase energy availability though in general more stress hormones will be released the longer the fasted or post absorptive state lasts for. This is called the catabolic state. However remember that this doesn’t automatically mean muscle loss. Catabolism of fat for example can occur rapidly with AMPK activation. Significant catabolism of muscle will only occur once amino acid pool in the liver has been depleted.
One of AMPK’s key actions is to preserve muscle tissue whilst aiding fat use as fuel.
In general the longer away from a meal the lower the blood levels or tonic levels of insulin are and the higher the levels of glucagon. More fatty acids are broken down in the fasted state and the lower levels of insulin encourage this process to be more effective. It’s important to remember though there’s never really an ‘on’ and ‘off’ switch we simply have a greater amount of these systems switched on or off at any given time depending in the main part on our energy balance.
So the fed states is about storing, recovering, building, switching on muscle protein synthesis resting and digesting. The fasted state is about mobilising energy, breaking down fats and even proteins for energy and if needed and the fight or flight response. Some people have labelled these states as per there master enzyme drivers.
The fasted state is sometimes labelled as the AMPK state (AMP-activated protein kinase). AMPK is a cellular energy sensor that serves to enhance energy availability = blunts energy consuming processes. There’s AMPK sensors in the brain (hypothalamus) and muscles. The effects these have on metabolism are quite different, more on this below. In short muscle AMPK is generally a good thing and levels when raised in brain can make life harder.
When AMPK levels raise in the hypothalamus you get more hungry, the brain signals the body to produce less heat thereby lowering metabolism and energy output. Compounds which can keep AMPK levels lower thereby keeping appetite lower and preventing a decline in metabolic activity include quercetin, ketones including raspberry ketones, nicotine and alpha lipoic acid. Alpha lipoic acid also increases muscle AMPK signalling and glucose transport mechanisms within muscle tissue. In general if we can keep the muscle effects of AMPK without excessive activation of brain AMPK we can ride the seesaw for longer with better adherence and a lower impact of overall metabolism from restricting energy balance.
To begin to understand this enzyme one way is to see the activation effects the drug metformin has on increasing AMPK in all cells. Metformin acts to lower glucose production in the liver thereby reducing energy signalling to all cells. In theory then any actions and compounds to assist lower energy delivery to cells or faster disposal of glucose should help with activating AMPK – when we look later at the foods, herbs and compounds which help we can see they often have an action related to these mechanisms.
Goat’s Rue is the herb which metformin is based upon.
AMPK then trigger the bodies survival mechanisms. In the muscle AMPK is a powerful stimulator for adaptation, antioxidant enzyme activity – increased mitochondrial biogenesis, increased insulin sensitivity – generally increasing fitness capacity, protection against oxidative stress and increasing sensitivity to sugar, thereby lowering insulin resistance.
In a low energy and substrate availability environment, this state the body can go into a phase of autophagy, which is where it breaks down and cleans up proteins. AMPK can facilitate entry into this state. Obviously anyone seeking to gain lean mass needs to consider the time spent in this phase needs to be balanced with time spent in the opposite phase the mTOR phase. Note fantastic gains can be made using intermittent fasting probably because of the rebound anabolic effect of fasting and feasting in a strategic manner.
The balance between anabolic and catabolic states needs to be balanced with the individual needs and performance requirements.
mTor or target of rapamycin (mTOR) is a serine/threonine kinase that plays important roles in cell growth and metabolism. It’s a building enzyme.One spoken about frequently in the supplement world as it’s in part regulated or switched on by amino acid availability in particular the amino acid leucine. To grow muscle we need to active this pathway as efficiently and often as possible.
Given the benefits of fasting and AMPK we are learning about now, It may be best to active this within a smaller time frame for overall health reasons. As with many things it’s a goal driven process deciding which pathways to emphasize and activate at any given time.
(taken from suppversity an excellent place to gen up on performance related science)….
Now here’s the part which start to get interesting and specific to health and performance. If we use a see saw approach combined with certain nutrients which help support these pathways we see a potential enhancement of each phase of metabolism.
For example, as discussed above, the active constituent of grapefruits has been shown to increase glucose uptake in cells. This is because Naringenin increases the AMPK mechanism, which becomes active once fuel supply is low in cells. Similarly, upon taking a certain amount of naringenin in, insulin activity is boosted. So we see here by underfeeding and taking certain nutrients we can reload more efficiently afterwards. This is sometimes called the anabolic rebound.
By stimulating certain pathways often the opposing pathway can become more active resulting in greater replenishment in a shorter period of time.
So as we begin to understand this enzyme we can see it’s activity can be provoked through lowering available energy in the cells and blood stream. As such nutrients which support glucose disposal could in effect help to smooth the pathway towards triggering more efficient AMPK release. Indeed insulin resistance would appear to hamper AMPKs effects somewhat. The relationship with metabolic disease AMPK and lower SIRT1 release is clear.
This is one of the reasons why the feasting and fasting methods of dieting for fat loss and over feeding for muscle growth have been so interesting for the body conscious training enthusiasts is these pathways tie in directly with healthy aging practices. You see the problem about aging is the mTOR and insulin, IGF1 pathways tend to be increasing associated with faster cell turnover (hence aging) and also in faulty cells this faster turnover predisposes people to an increased driver for cancer formation.
In the fasted state the AMPK and sirt (class III protein deacetylase) not only activate autophage where cancerous cells can be cleaned up and broken down out of the body, they also increase insulin sensitivity which maybe one way to slow down lifetime insulin production which maybe another method by which we accelerate aging. So we have if you like an AMPK / MTOR see saw effect which we need to ride carefully. Both are essential to life but riding each pathway in excess has downsides particularly as we age when cells behave less like they ought to.
Ways to keep brain AMPK lower and muscle AMPK higher….
Regulating the hypothalamus from an AMPK, inflammation and hunger hormone perspective is essential to maintaining resistance from cravings, keeping metabolic rate high, sustaining the metabolism signals for the fat to keep burning and not making you so hungry you can’t continue to make the right food choices.
The solution? Introduce a hormetic dose of each system in a fashion which fits your age and training goals and requirements. The hormetic dose means the amount of an action or compound which stimulates, allowing sufficient adaptive responses to occur without compromising the hosts adaptive capacity. The obvious example is the training, super compensation model, less obvious examples can be found in the adaptogenic herbal research areas and more recently in the nuerohormetic research papers talked about and listed below where a small dose of a strong flavonoid or phytochemical can have a profound protective effect in the host.
An example of a hormetic dose of training would be enough to damage tissues and begin the adaptive response, without continuing to tax this region and build stress on stress in the area. In other words if you continued try to provoke a muscle group before it’s sufficiently recovered we would move into a non-adaptive response setting. With something like intermittent fasting this would mean an excessive release of stress hormones and more catabolic processes in place over anabolic, a gradual loss of mass and depletion of stress reserve would ensue. In terms of mTOR in aging, insufficient stimulation would result in loss of lean mass something we want to avoid as we age, over stimulation could in theory lead to higher incidence and almost certainly faster progression of existing cancers. Just the right amount would keep muscle whilst allowing for autophagy to keep the cells clean and healthy.
Fast mimicking compounds and foods;
This list is comprehensive but there maybe be certain items which are also useful which are not listed here. As AMPK and fasting are so good for overall health I’ve included some items which can help rejuvenate mitochondrial health, as well as insulin supporting and direct AMPK stimulating factors. I’ll start with broad brush approach and dial it into specific compounds and supplement recommendations further on. I’ve added links to the studies and sources of some of this information if you want to look up the compounds in more detail and have a general read around the subject.
Things which will help;
- All SIRT1 foods – which is basically anything with a high antioxidant or polyphenol content.
- Omega 3 fats. Especially when combined with a higher polyphenol rich diet.
- Anything which helps lower inflammation, this includes the polyphenols and omegas listed above, plus herbs such as curcumin, boswellia and so on.
- Resveratrol, pine bark extract, all NO2 boosters including aminos such as arginine and citrulline.
- Green tea and green tea extract. Roobosh tea.
- Insulin mimicking and supporting nutrients, including alpha lipoic acid, vanadyl sulphate, blueberry extract, bitter melon, cinnamon extract, gymnemma….
- To support mitochondrial biogenesis; Co Q 10, PQQ….
Berberine, salicylate (white willow bark),
Synergy is often more efficacious than using single source supplementation for example combining resveratrol with quercetin appears to have additive effects.
It can be common to get a little hungry when you are first getting used to fasting. Keeping fluids up is really important, using a little salt or electrolytes also can help, especially if you get dizzy or headaches. Green tea or weak coffees, including decaf are helpful also. Many people find 5HTP really effective to reduce cravings, and you can also use a little glutamine, inositol and glycine to help – these taste slightly sweet also. Prudent use of ketones in fasting phases can be of use to some people, however taking some coconut oil or MCT’s probably has a similar and cheaper effect on appetite suppression and maintaining ketosis.
Training support. Training while fasting can be hard especially if you train before your feeding window. Using aminos to support training and supply some energy and muscle support is a good idea. Amino acid formulas need to contain the full spectrum of essential amino acids, exercise specific support e.g. taurine / betaine and additional metabolic supporting cofactors. Metabolic Amino Complex is an example of a fully comprehensive low calorie formula to fulfill this requirement.
Example Day – here’s part of a client programme to rebuild brain function following an early onset stroke;
Programme will revolve around;
- Learning new tasks
- Supporting siesta to consolidate learning when possible
- Use of fasting and ketones to assist neuro-regeneration
- Specifically increasing certain foods and herbs in day to day cooking
- Avoiding alcohol (expect moderate), stress and neurotoxins wherever possible
- Increase exercise, sunlight and sleep support
- Regular sex (when possible)!
- Semi-ketotic diet and use of ketones / ketosis, fast mimicking compounds and supplements.
- High omega 3 intake
- Alternative therapies e.g. oxygen and ozone
NGF and BGFN these 2 growth factors are required for increase neurogenesis. For further reading please click here.
- R5 Aminos; Use 1-2 times daily after exercise and with supper
- Focus Formula; Use in morning before learning session number 1.
- Compounds vs insulin resistance; various but focus on berberine and guggle. Get Metabolic Optimizer.
- Fish Oil; take 2-3 fish oil capsules daily.
- Phospholipids like Lecithin; Use in a daily power shake.
- Nootropics; consider both noopept and piracetam
- Prebiotics and probiotics; use and cycle these
- Neurohometic foods; Read the document and include and cycle foods and supplementation
- Exogenous Ketones; use daily. Do ‘reset’ once per month 60 hour fast.
- Curcumin; take 2-4 capsules daily and use in food regularly.
- Gugglesterones; cycle for 4 weeks on at first and then 2 weeks on, 1 week off.
- Berberine; Use Daily.
- Green tea; Use daily as drink and cycle as a supplement.
Suggest following approximate daily routine.
- Wake Up;
- Coffee + supplements.
- COLD THERAPY easy in the pool in Spain. Otherwise find some cold water or take a long cold shower.
- Daily learning 30-40 minutes. Language or memory training. Rest 20 minutes
- Repeat if time 30-40 minutes; different activity.
- AM Shake;
- Ketones or coconut oil / MCT’s + R5 aminos + berries + fats (coconut and fish oil) + curcumin.
Suggested daily at least 60 minutes. Needs to be HIIT or aerobic for best brain effect.
Post exercise; Aminos as recovery (use blend) + probiotics + fibre (chia seeds) and lecithin. Special Loader Recommended.
Or take small protein only breakfast. Aim to match 50% of exercise calories.
AM; Working / projects / meetings.
- Fast until 2-6pm. Then lunch as per 4WFL macros 2:1:1
- E.g. Bone broth + prawns
- Or protein salad.
AFTERNOON SLEEP; important. Try and get at least 30 minutes when possible.
- Decaf coffee / green tea / fluids.
- PM; Working / projects / meetings.
- PM exercise; specific body part e.g. abs / sauna. Learning e.g. Musical Instrument
- Largest of the day to fit with social.
We will also have periods of lower calorie intake at this time and load calories up at lunchtime and potentially in the morning also. E.g. once per month 5 days of PM meals only.
High polyphenol intake in general.
The metabolic optimizer has many of the AMPK herbs listed. In addition to this it would be worth getting a mitochondrial energy optimizer or looking at some key nutrients for mitochondrial energy function. Co Q 10, Alpha Lipoic Acid and acetyl – l – carnitine are key areas, DMAE is very good as part of the focus formula blend.
Metabolic optimizer ingredients are listed below with references;
Inflammation and AMPK
Nutrients and habits which support a lower energy environment will support higher levels of AMPK…
FASTING OPTIONS AND GOALS – PRACTICAL PROTOCOLS
Starving your cells, and exercising at least some of the time, makes them super good at using fat as a source of fuel. Higher intensity fueled training is essential for maximum performance adaptations.
1-2 days per week on 500-600 calories. Easy to pick days to clear from social and other food related meetings. Choosing lean proteins and salad vegetables makes the evening meal nourishing and fulfilling. Establishes a deficit which has benefits over time.
Daily fasting – feeding windows. 16:8 with 16 hours fasting and 8 hours feeding. These protocols help but in the end they all depend on the quality and overall calories consumed in the feeding window for success. You still need to eat healthy, meet protein requirements and establish and overall deficit if fat loss is a goal (which it is for 80% of people). The limited feeding window does make it harder to over consume calories and the fasting window does rest the system and bring about some benefits.
This system works best when combined with exercise. For example feeding 9-6pm. With a PM exercise session at 9pm and an AM exercise session at 6am makes this a very effective fat loss / fitness strategy. If you keep to the magic macros ™ during the feeding window of 2:1:1 then this further enhances the overall deficit. Aminos are recommended throughout the workout to support exercise capacity and mental energy.
If you think about it following the 2:1:1 causes a lower energy environment, capping that off with a PM workout and then aminos triggers all the autophagy processes. Doing another session in the AM Further enhances fat burning and fitness adaptations. It’s hard – but it’s worth it.
The 18:6 pattern lends itself nicely to an extended morning fast with a late lunch at say 2pm. Then the final meal being finished by 8pm. You can of course bring this to an 10am breakfast and 4pm last meal – it all depends on your social patterns, family and making the feeding fit your sustainability factors.
When we then look at 20:4 or 22:2 then we are really looking at one or two feeding meals within a short period. This is more akin to daily calorie restriction and lends itself nicely to maintaining and very low calorie diet (VLCD). This can be good for rapid cuts in fat weight but would be much harder or near impossible to maintain higher levels of performance based activity. It could be good for general lower level endurance activity though.
How your body composition alters around fasting really does depend on your overall 24 hour and weekly calorie deficit, macro nutrient ratios also play a part – however the essential element is to retain a base level of protein intake to sustain your lean muscle mass.
If you match your energy requirements in the feeding window you should, combined with training and the right macro nutrient split achieve a better body composition at roughly the same weight. Keeping a deficit in the feeding window whilst maintaining the 2g/PRO per kg should result in pure fat loss with retaining lean tissue. It’s best not to go too far below your BMR(magic macros work out to BMR when you are close to your lean mass) – basal metabolic rate for more than 3-4 days, outside of medical fasting before strategic carb refeeding.
When you work out your macros ideally you aim for your desired lean weight, rather than your actual weight. Except if you are quite lean or within say 5% of your ideal body fat then you can go off actual weight. For example an 80kg 20% body fat and work out macros based on their actual weight. A 150kg @ 50% body fat female who has an ideal body weight of 65kg @ 20% fat should work off 65-70kg multipliers or they will be eating 300g of protein and their macros and calories would come out too high to allow fast fat loss.
CLA and resveratrol
Neurohormetic phytochemicals: An evolutionaryebioenergetic perspective
Vikneswaran Murugaiyah a, Mark P. Mattson b, * a School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia
b Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA
Factors Involved in Insulin Management and Glucose Disposal
NOTES AND ADDITIONAL USEFUL DIAGRAMS