Best Anti-aging supplements other than NR and NMN

22 Best Anti-Aging Supplements

Geroprotectors are substances that support healthy aging, slow aging, or extend healthy life. Sometimes people refer to them as “aging suppressants,” “anti-aging drugs,” “gerosuppressants,” “longevity therapeutics,” “senolytics,” or “senotherapeutics.” They include various foods, nutraceuticals (supplements), and pharmaceuticals (drugs). Unfortunately none comes close to realizing the age-old aspiration of ending aging altogether (yet), but some may make a practical difference for many people.

I’ve used several geroprotectors for years. And I’m exploring ways to incorporate others into my diet, if they’re applicable to my personal situation and meet a few general criteria:

First, I look for geroprotectors supported by multiple studies on humans – not just anecdotal evidence, one study, or studies on non-human animals. Although I’ve nothing against the health benefits of placebo, I prefer knowing that something more than only placebo is at work.

Second, I look for geroprotectors with the highest ratios of efficacy to expense. Given innumerable options and a limited budget, I want to do more than just empty my wallet.

Third, I look for geroprotectors that are legal and generally safe. If it’ll put me in a hospital or a prison, it’s not worth it.

Based on those criteria, I’ve compiled a list of top tier natural geroprotectors. These are, to the best of my knowledge, the most well-researched and effective geroprotectors available in the United States without a prescription. I’ve excluded from this list any geroprotectors that are primarily nootropic geroprotectors (such as ginkgo and melatonin), which you can find in my list of top tier nootropics. This information is for educational purposes only. It is not medical advice. Please consult a physician before and during use of these and other geroprotectors.

1) Berberine


Berberine is a compound of extracts from herbs such as barberry. Supplementation may provide a strong decrease to blood glucose, and a notable decrease to total cholesterol, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Berberine may also provide a subtle increase to HDL-C; and a subtle decrease to insulin, LDL-C, and triglycerides. Evidence for these effects may not be as reliable. See the Berberine article  for more studies and details.

2) Blueberry


Blueberry is the fruit of a perennial flowering plant native to North America. Supplementation may provide a notable decrease to DNA damage, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

See the Blueberry article at for more studies and details.

3) Boswellia Serrata (Frankincense)


Boswellia Serrata is a plant native to India and Pakistan. Supplementation may provide notable support for long-term joint function, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

See the Boswellia Serrata article at for more studies and details.

4) Cocoa


Cocoa comes from the seeds of evergreen trees native to tropical regions of Central and South America. Supplementation may provide a notable increase to blood flow, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Cocoa may also provide a subtle increase to insulin sensitivity, and photoprotection; and a subtle decrease to general oxidation, platelet aggregation, and LDL-C. Evidence for these effects may not be as reliable.

5) Coenzyme Q10

Coenzyme Q10

Coenzyme Q10 is a molecule found in the mitochondria of humans and other organisms. Supplementation may provide a notable decrease to lipid peroxidation, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Coenzyme Q10 may also provide a subtle increase to blood flow, endothelial function, and exercise capacity; and a subtle decrease to blood pressure, exercise-induced oxidation, and general oxidation. Evidence for these effects may not be as reliable. See the Coenzyme Q10 article at for more studies and details.

6) Creatine


Creatine is a nitrogenous organic acid that occurs naturally in vertebrates. Supplementation may provide a strong increase to power output and a notable increase to hydration, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Creatine may also provide a subtle increase to anaerobic running capacity, lean mass, bone mineral density, muscular endurance, testosterone, VO2 max, and glycogen resynthesis; and a subtle decrease to blood glucose, lipid peroxidation, and muscle damage. Evidence for these effects may not be as reliable. See the Creatine article at for more studies and details.

7) Curcumin


Curcumin is the bioactive in Turmeric, which is a perennial plant native to Southern Asia. Supplementation may provide a notable increase to antioxidant enzyme profile and a notable decrease to inflammation and pain, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Curcumin may also provide a subtle increase to HDL-C, and functionality in the elderly or injured; a subtle decrease to blood pressure, general oxidation, lipid peroxidation, and triglycerides; and subtle support for long-term joint function. Evidence for these effects may not be as reliable. See the Curcumin article for more studies and details.

8) DHEA (Dehydroepiandrosterone)


DHEA is a natural hormone in humans and other animals. Supplementation may provide a notable increase to estrogen or testosterone (depending on the need of the body), according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

See the Dehydroepiandrosterone article at for more studies and details.

9) Fish Oil


Fish Oil, as the name suggests, is an oil that accumulates in the tissues of some fish species. Supplementation may provide a strong decrease to triglycerides, thereby supporting a healthy cardiovascular system, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Fish Oil may also provide a subtle increase HDL-C, endothelial function, and photoprotection; and a subtle decrease to blood pressure, inflammation, natural killer cell activity, platelet aggregation, and LDL-C. Evidence for these effects may not be as reliable. See the Fish Oil article at for more studies and details.

10) Garlic


Garlic is a bulbous plant native to Central Asia. Supplementation may provide a notable increase to HDL-C and a notable decrease to LDL-C, total cholesterol, and blood pressure, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Garlic may also provide a subtle decrease to triglycerides and a strong decrease to rate of sickness. Evidence for these effects may not be as reliable. See the Garlic article at for more studies and details.

11) Horse Chestnut (Aesculus Hippocastanum)

Horse Chestnut

Horse Chestnut is a deciduous flowering tree native to South East Europe. Supplementation may provide notable support to long-term circulatory function, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Horse Chestnut may also provide a subtle decrease to pain. Evidence for this effect may not be as reliable. See the Horse Chestnut article at for more studies and details.

12) Magnesium


Magnesium is an essential dietary mineral found in food like nuts, cereals, and vegetables. Supplementation may provide a notable decrease to blood pressure (only in cases of high blood pressure), according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Magnesium may also provide a subtle increase to insulin sensitivity, aerobic exercise, and muscle oxygenation; and a subtle decrease to blood glucose, and insulin. Evidence for these effects may not be as reliable. See the Magnesium article at for more studies and details. also check out my article on Magnesium Glycinate supplementation. Magnesium is an ingredient in Thrivous Serenity.

13) Nitrate


Nitrate is a molecule produced in the body in small amounts and available in vegetables like beetroot. Supplementation may provide a notable decrease to blood pressure, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Nitrate may also provide a notable increase to anaerobic running capacity; and a notable decrease to oxygenation cost of exercise. Evidence for these effects may not be as reliable.

14) Olive Leaf

Olive Leaf

Olive Leaf comes from an evergreen tree native to the Mediterranean, Africa, and Asia. Supplementation may provide a notable decrease to blood pressure and oxidation of LDL, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Olive Leaf may also provide a subtle increase to HDL-C; and a subtle decrease to LDL-C, total cholesterol, cell adhesion factors, and DNA damage. Evidence for these effects may not be as reliable. See the Olive Leaf Extract article at for more studies and details.

15) Pycnogenol (Pine Bark)

Maritime Pine

Pycnogenol is an extract from bark of the maritime pine, native to the Mediterranean. Supplementation may provide a notable increase to blood flow, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Pycnogenol may also provide a subtle decrease to leg swelling; and subtle support for long-term joint function. Evidence for these effects may not be as reliable. See the Pycnogenol article at for more studies and details.

16) Salacia Reticulata

Salacia Reticulata

[“Kothala Himbutu” by under CC BY-SA 3.0 / cropped]

Salacia Reticulata is a plant native to the forests of Sri Lanka. Supplementation may provide a notable decrease to blood glucose and insulin, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

See the Salacia Reticulata article at for more studies and details.

17) SAMe (S-Adenosyl Methionine)


SAMe is a naturally-occurring compound found in most tissues and fluids of the human body. Supplementation may provide notable support for long-term joint function, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with SAMe may also provide a subtle increase to functionality in elderly or injured; and a notable decrease to pain. Evidence for these effects may not be as reliable. See the S-Adenosyl Methionine article at for more studies and details.

18) Spirulina


[“Spirulina” by Lara Torvi under CC BY 2.0 / cropped]

Spirulina is a blue-green algae. Supplementation may provide a notable decrease to lipid peroxidation and triglycerides, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Spirulina may also provide a strong decrease to allergies, nasal congestion, and liver fat; a notable increase to power output; a notable decrease to blood pressure and general oxidation; a subtle increase to HDL-C and muscular endurance; and a subtle decrease to LDL-C and total cholesterol. Evidence for these effects may not be as reliable. See the Spirulina article at for more studies and details.

19) TUDCA (Tauroursodeoxycholic Acid)


TUDCA is a bile acid found naturally in trace amounts in humans and in large amounts in other animals like bears. Supplementation may provide a notable decrease to liver enzymes, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with TUDCA may also provide a notable increase to insulin sensitivity. Evidence for this effect may not be as reliable. See the Tauroursodeoxycholic Acid article at for more studies and details.

20) Vitamin B3 (Niacin)


Vitamin B3, also known as Niacin, is an essential dietary vitamin found in foods like liver, chicken, beef, fish, peanuts, cereals, and legumes. Supplementation may provide a strong increase to HDL-C and a notable decrease to LDL-C and triglycerides, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Vitamin B3 may also provide a subtle increase to blood glucose and insulin; and a subtle decrease to insulin sensitivity and vLDL-C. Evidence for some of these effects may not be as reliable. See the Vitamin B3 article at for more studies and details.

21) Vitamin D

Vitamin D3

Vitamin D is an essential dietary vitamin naturally synthesized in the skin from sun exposure. Supplementation may provide a notable decrease to risk of falls, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Vitamin D may also provide a notable increase to functionality in elderly or injured; and a subtle decrease to blood pressure, bone fracture risk, and fat mass. Evidence for some of these effects may not be as reliable. See the Vitamin D article at for more studies and details.

22) Vitamin K

Vitamin K1

Vitamin K is an essential dietary vitamin found in foods like leafy green vegetables and some fruits. Supplementation may provide a notable increase to bone mineral density, according to multiple peer-reviewed, double-blind, placebo-controlled studies in humans:

Supplementation with Vitamin K may also provide a notable decrease to bone fracture risk. Evidence for this effect may not be as reliable. See the Vitamin K article at for more studies and details.

5 Day Fast – Using the Fast Mimicking Diet

Recently I began a 3-day fast, which then got extended to 5 days.

The intention was to use the “Tim Ferriss method” (described here). Essentially accelerating the shift from glucose burning to fat burning as quick as possible, avoiding the negative physical feelings associated with the transition period. (60 second video primer on ketones if you’re not familiar).

However, in the process of researching more about the measurement of blood glucose and blood ketones, I realised its possible to experiment a bit.

There has been some excellent research done by Valter Longo and his colleagues at the University of Southern California on a way to do fasts, without completely stopping eating.

Essentially, they were aware of all the health benefits associated with fasting, but wanted to tackle the problem of compliance. For most people these days, the thought of not eating for 5 days is too much to handle.

They have come up with a 5 day diet that is low enough in calories and carbohydrates, that the user gets the vast majority of the benefits from fasting.

Actually, they have patented their specific diet as – and are selling it to hospitals to prescribe to their patients. Your first thought is probably…huh? But its more about “playing the game”, and finding ways to get fasting into hospitals, than it is about money. I believe Valter has even gone as far as to pledge his profits from the endeavour to charity. For more on Valter Longo and the FMD diet – check out Rhonda Patrick’s podcast with him.

What patients would find when they use the prescription Prolon diet

Luckily for us, we can use Valter’s research into fasting, without getting a prescription for his diet. In the paper that they published to, they describe the details of the diet:

The human FMD diet consists of a 5 day regimen:
– Day 1 of the diet supplies 1,090 kcal (10% protein, 56% fat, 34% carbohydrate)
– Days 2–5 are identical in formulation and provide 725 kcal (9% protein, 44% fat, 47% carbohydrate).

Damien, of Quantified Body figured out that this is similar to the macronutrient composition of avocados. So for example, you could have 2 medium sized avocados per day on each of the 5 days.

It doesn’t have to be avocados though, it could be anything that fits the above macros.

The other interesting piece of the puzzle, that contributed to this fast, was a paper by Dr Seyfried on treating brain cancer.

They found that if they could keep patients in what they termed “nutritional ketosis”, then they could achieve remission in some patients. Nutritional ketosis differs from simply measuring blood ketone levels, instead it measures the ratio between blood glucose and blood ketones. I’ve written in more detail here about it.

The sweet spot where blood glucose drops and blood ketones rise. This graph comes from Seyfried’s experiment to halt tumor growth.

My 5 Day Fast Details

The crux of my experiment, is that adding in some calories/nutrition makes the whole process MUCH easier. And you can do it in a calculated way.

Here’s the rough breakdown of what I consumed:

  • Day 1 (after 24h) – 2 tablespoons of MCT oil (C8)
  • Day 2 – 2 tablespoons of MCT oil (C8) + 1 tablespoon of coconut oil
  • Day 3 – 1 avocado (with Himalayan sea salt + apple cider vinegar) + 1 tablespoon of coconut oil
  • Day 4 – 2 avocados (again with Himalayan sea and apple cider vinegar) + 1 tablespoon of coconut oil + 1 tablespoon of MCT oil (C8)
  • Day 5 – Nothing until I broke the fast in the evening

You can see I didn’t adhere strictly to the fast mimicking diet, and was generally under the prescribed amount of calories. But was far in excess of a simple water fast.

From the end of day 1, my ketones were elevated (no doubt helped by the MCT oil). Highest they reached was about 4.4mmol/L, with blood glucose simultaneously at 2.8mmol/L.

2.8 mmol/L blood glucose reading (about 39 mg/dL)


4.4 mmol/L blood ketone

The measurement of blood ketones and blood glucose come in useful for 3 main things:

  1. Tracking your transition into ketosis – and correlating how you feel with where you are in ketosis
  2. Giving you a measurable goal to aim for and maintain! (this is huge)
  3. You can use the blood measurements to test how different foods / ketone sources affect them

Regarding #3 – when I ate the second avocado on day 3, my bloods actually showed I came out of nutritional ketosis. Even though my ketones were at 2.5 mmol/L, my blood glucose was at 4.3 mmol/L. Which is a ratio of 1.72 – rather than the desired ratio of 1.0 or lower.

After Thoughts

All in all this experiment was a success.

Its becoming increasingly more obvious that fasting is an important tool in humanities arsenal against disease. Once upon a time, as hunter and gatherers, these fasted states were forced on us by the environment. Now in today’s abundant first world, we have to artificially create them. As with any “medicine”, one of the big hurdles is compliance.

The last 5 day fast I did was back in November, and it was taxing to say the least. I certainly didn’t feel in a rush to do another one. However, this time around, I felt much more functional throughout the fast – and can see a way to make this a more regular thing. Regular being something in the order of twice per year.

Exiting The Fast + Ketosis

Probably the worst part of the fast this time was the exit. I think it comes down to the harsh way I went from nutritional ketosis, to consuming reasonably high levels of carbohydrates. In retrospect, I’d probably prepare a meal with some fatty meat + vegetables. That way it fulfils the need I have to *eat everything*, but won’t cause such a harsh crash after.

I’ve never been a strong believer in living in ketosis, and I’m still not. But there’s something about seeing the effect on your body when it goes from ketosis to glucose burning, that makes you question if you’re doing it a favour!

Further Questions

There’s a few points from this experiment I’d like to learn more about:

  • Evening of day 3 I was still producing ketones, but out of nutritional ketosis. Morning of day 4 I was back in nutritional ketosis. What effect does coming out of nutritional ketosis have on the overall efficacy of the fast?
  • If we were to compare a completely water based fast, to the fast mimicking diet, what are we losing out on?
  • If we are losing out on something, could this be mitigated by going to 6 or 7 days?

Anyway, that’s a rather large brain dump. Hopefully if you’ve got this far you’ve been able to extract some nuggets to help you in your journey. If you’ve got any questions or comments, please leave them below. As for any blogger, feedback is wonderful.

Detox diets: Do they work?

Detox diets are another way to clean, clear and cleanse your body. It is a popularize way commonplace , mainstream and more and more acceptable, toted and advocated as the thing to do for and with your body to ensure health. IT IS NOT ABOUT LOSING WEIGHT PER SE AS THE FIRST AND FOREMOST GOAL, yet people do tend to lose weight while getting rid of the toxin build up. You are invited and encouraged to partake of natural and healthy foods MORE often, rather than unhealthy, empty calorie consumption of unhealthy foods and snacks. Typically detoxification procedures involve liquid type diets and pretty much nothing else, initially and generally systematically introduces back into the diet, the other foods and chemicals again, to ensure that your body is back in balance and healthy. You can have shock and withdrawal, even cravings while on the DETOX.

Here are some positive ways DETOX can contribute and have an effect on your life, healthand body:

  • A detoxification process and cleansing can do a lot for you – there are many benefits and rewards, including added energy, generally feeling healthier with more vitality and spunk.
  • It is toted to cure, prevent diseases, keep you focused and energized.
  • These positive effects some attribute to the effective and total elimination of toxins and harmful build-up of certain substances in your body that is broken down and gotten rid of.
  • Mostly these types of interventions are supposedly short to medium term and not stuck to for an extended period.
  • AGAIN, IT NEEDS TO BE EMPHASIZED, THAT DETOX IS NOT A WEIGHT LOSS TOOL FIRST AND FOREMOST (although some have been highly effective in losing weight while detoxifying their bodies).


– Fasting, restrictive diets
– Not seen as suitable for young growing children or athletic or highly active teens
– Diabetics and/or less than optimal healthy individuals should proceed with caution PRIOR to detoxifying for any extent of time.
– The euphoria and rewards you experience while and after detoxifying, could very easily have you wanting more and doing it again and again.
– Extreme caution is advised, as it could be detrimental to your health and well-being if this became your lifestyle.
– Taking laxatives (sometimes part of the processes suggested) might lead to some, any or all of the following:
– other complications
– mineral imbalances
– digestive system issues
– dehydration
– Addictive type behaviors and bad habits
– Water and muscles loss over time
– slowing down your metabolism
– losing , maintaining and controlling weight could become MORE difficult
– Balanced living and healthy nutrition needs to prevail. These processes demand you eat healthy foods like:

– lean meats
– eggs
– beans, or peas
– calcium
– low-fat or fat-free milk
– yogurt
– lots of water daily
– fiber
– fruits
– veggies
… and many others.

You will experience the MOST success initially and in the beginning of your detoxification process, as your body re-establishes its original and preferred balance – its optimal, ultimate state and functioning! But it does depend on each unique individual, as no two people will have the same experience with DETOX.

Things to bear in mind to optimize your DETOX:

– In general to boost the effectiveness and results of this procedure and treatment,
avoid caffeine, sugar, fried fatty foods, soda drinks and alcohol directly following and a couple of days after. YOU WILL SEE AND FEEL THE DIFFERENCE.
– It can be messy and take long, so divert your attention and make it practical and comfortable
– Stay hydrated and you can even take a shower before the procedure in order to prepare your skin for what is to come
– Thermal blankets can enhance the experience and wrapping somewhat tight (NOT TOO TIGHT) can do the trick!

Many Medications, supplements and other herbal, natural products to consider for detoxification
Apart from naturally occurring nutrients and good detox-enablers, like:
Whole foods
other natural products and substances
Fresh fruits and vegetables
Greens or phytochemical-rich foods and groups
Foods that protect you against cancer, heart disease, diabetes and high blood pressure:
– antioxidants
– there are also supplements and pills to consider – also for DETOX processes and results.
In In our pop the pill type culture and habits, it is so easy to think that there is a magic bullet for everything. A tablet or capsule, gel-tab, mixture or potion for everything under the sun – ailment and cure!

Sometimes we do not eat enough, eat the wrong things, too much, not a balanced diet, food on the run, and then take multivitamins and mineral supplements to ensure that we get our daily dose of what our bodies require. Others who may benefit include seniors and pregnant women.

TIPS and recommendations for choosing, using and tapping into natural or herbal supplements for DETOX and healthy living

– Be SMART about which ones you take when
– Be sure to check the expiration dates to ensure potency and results
– Do not overdose or take more than the recommended amount  DO NOT USE EXPIRED products.
– Ensure you know the source, manufacturer, contents, label
– High doses of certain elements can have negative effects on the body
– Interference and interactions with other things that you might be taking
– List the active ingredients and all other fillers, additions or other ingredients nutrients and dosage
– Look at the details on the label regarding its strength, purity, disintegration and dissolution.
– Marketing ploys, promises and packaging is not what you end up putting in your body – treat with skepticism, care and caution.
– Serving, size and storage
– Store and keep out of reach of children, non-humid and high-up is best.
– Supplements may not be suitable for all individuals, those suffering from certain illnesses.
– They are BEST taken in addition to diet and nutrients, NOT MERELY AS substitutes.
– They are not good replacements for real food.
– You need to know what and why you are taking supplements

In the environments we live and function in, there are many contaminants present that we need to cope and deal with effectively to avoid their build up interfering with our health, well-being, longevity and balance. WE need to rid our systems and bodies of it and this is often called detoxification as we have seen. Anyone and everyone can do it, if you proceed with caution. Polluted air, additives in our foods, pesticides on our fruits and veggies, genetically altered food and more need to be clean, cleared and cleansed from our systems, tissue and being!

Fasting decreases hunger which makes it more effective than dieting

Ghrelin is the so-called hunger hormone, first purified from rat stomach in 1999 and subsequently cloned. It binds to growth hormone (GH) secretagogue receptor, which strongly stimulates GH. So, eating, by itself does not makes you gain lean tissue (like muscle and bone), despite what all the makers of supplements like whey protein and creatine claim. Rather, hunger may be a strong growth stimulus.

Nothing turns off Growth Hormone like eating and you need GH to grow functional tissue. Of course, food provides the nutrients needed to grow, so in fact, you need both feeding and fasting cycles to properly grow. Not all feeding, and not all fasting. Life lies in the balance of the two. The cycle of life is feast and fast. But in today’s world, many people would have you believe that fasting is detrimental to your health, and that you should eat all the time.

The biggest worry about fasting is dealing with hunger. People assume that hunger will get worse and worse until you cannot help yourself and start an IV donut slurry in your garage. Oooh… donuts…. Ghrelin, the hunger hormone, increases appetite and weight gain. It also antagonizes the effect of leptin (in rats at least). Leptin is a hormone produced by fat cells which turns off appetite and makes us stop eating.

Ghrelin turns on appetite. So, if you want to lose weight on a long term basis, you need to tune down ghrelin. If you don’t eat (fast), don’t you get hungrier and hungrier, ghrelin goes up and up and you’ll just gain weight?

Well, no. As we discussed last week, eating all the time sounds like it will turn off hunger and ghrelin. But that’s far too simplistic. Surprisingly, the answer to turning down ghrelin (and hunger) is the opposite — fasting.

Let’s look at this study “Spontaneous 24-h ghrelin secretion pattern in fasting subjects“. Patients undertook a 33 hour fast, and ghrelin was measured every 20 minutes. Here’s what ghrelin levels look like over time.

There are several things to notice. First, ghrelin levels are lowest at approximately 8:00 – 9:00 in the morning.

Circadian rhythm studies consistently find that hunger is lowest first thing in the morning, also generally the longest period of the day where you have not eaten.

This reinforces the fact that hunger is not simply a function of ‘not having eaten in a while’. At 9:00, you have not eaten for about 14 hours, yet you are the least hungry. Eating, remember, does not necessarily make you less hungry.

Next, notice that there are 3 distinct peaks corresponding to lunch, dinner and the next day’s breakfast. BUT IT DOES NOT CONTINUALLY INCREASE. After the initial wave of hunger, it recedes, even if you don’t eat.

Ghrelin shows a “spontaneous decrease after approximately 2 h without food consumption”. This correlates perfectly to our clinical experience in the Intensive Dietary Management Program that ‘hunger comes in waves’.

If you simply ignore it, it will disappear. Think of a time that you were too busy and worked right through lunch. At about 1:00 you were hungry, but if you just drank some tea, by 3:00 pm, you were no longer hungry. I often feel the same level of hunger whether I ate lunch or not — exactly what the ghrelin studies show. Ride the waves — it passes.

Also note that ghrelin does have a learned component since all these subjects were used to eating 3 meals per day. It is not merely by coincidence that these peaks of ghrelin happen. This is similar to the ‘cephalic phase’ of insulin secretion that we’ve discussed previously.

There was one other big finding of this study. Look at the average ghrelin levels over 24 hours. Over the entire day of fasting, ghrelin stays stable! In other words, eating nothing over 33 hours made you no more or less hungry than when you started! Whether you ate or did not eat, your hunger level stayed the same.

Eating more sometimes makes you more hungry, not less. In the same vein, eating less can actually make you less hungry. That’s terrific, because if you are less hungry, you will eat less, and are more likely to lose weight.

So what happens over multiple days of fasting? This study looked at the question specifically. 33 subjects had their ghrelin measured over 84 hours of fasting and they divided the results by men and women, as well as obese and lean.

There were no significant differences between the lean and obese subjects, so I won’t dwell on that further. Once again, there were distinct circadian variations.

Over 3 days of fasting, ghrelin gradually DECREASED. This means that patients were far LESS hungry despite not having eaten for the past 3 days. This jives perfectly with our clinical experience with hundreds of patients undergoing extended fasting in our IDM program.

Everybody expects to be ravenously hungry after fasting multiple days, but actually find that their hunger completely disappears.

They always come in saying ‘I can’t eat much anymore. I get full so fast. I think my stomach shrank’. That’s PERFECT, because if you are eating less but getting more full, you are going to be more likely to keep the weight off.


Notice, also the difference between men and women. There’s only a mild effect for men. But the women show a huge decrease in ghrelin. Again, this addresses one of the major worries that women are not able to fast.

Actually, women would be expected to have more benefit from fasting because their hunger can be expected to decrease better than men. Notice, too, how much higher women’s ghrelin level reaches.

I suspect this correlates to the clinical observation that many more women are ‘addicted’ to certain foods eg. chocoholics. Sugar addicts. etc.

So many women have remarked how a longer fast seemed to completely turn off those cravings. This is the physiologic reason why.

A few other notes about the hormonal changes of fasting. Notice that cortisol does go up during fasting.

Yes, fasting is a stress to the body and cortisol acts as general activator as well as trying to move glucose out of storage and into the blood. So, if too much cortisol is your problem, then fasting may not be right for you.

Insulin also goes down, which is what we expect. Growth hormone, as we’ve previously noted, goes up during fasting. This helps to maintain lean muscle tissue and to rebuild lost protein when you start to eat again.

An interesting study of food cravings found exactly what we have been discussing. When patients were put on low calorie diet (1200) versus very low calorie (500) diets, food cravings didn’t change much on the former, but virtually disappeared on the latter. Yes. By eating almost nothing, food cravings did not get worse, they got much, much better.
This effect on food cravings is true for all food, since all foods are restricted. So cravings for sweets, carbs and high fat foods are all reduced.
This is very important in the fight to lose weight. Controlling hunger by eating little bits at a time simply does not work.

During intermittent and extended fasting, ghrelin, the main hormonal mediator of hunger does not increase to unmanageable levels. Rather it decreases — which is exactly what we are looking for.

We want to eat less, but be more full. Fasting, unlike caloric restriction diets is the way to do that.

Keto Diet better than high carb for Type 2 diabetes

Type 2 diabetes is a common condition characterized by high levels of blood sugar, usually due to insulin resistance.

The treatment of type 2 diabetes involves medication, but lifestyle strategies are very important as well.

These include increased exercise, weight loss and diet management.

Although low-carb diets have become popular for managing type 2 diabetes, few high-quality studies have investigated their long-term effects on blood sugar control and risk factors for heart disease.

Low-Carb diets


A team of Australian researchers set out to compare the long-term health effects of a low-carb diet and a high-carb diet, focusing on differences in blood sugar control and risk factors for heart disease.

Tay et al. Comparison of Low- and High-Carbohydrate Diets for Type 2 Diabetes Management: A Randomized Trial. American Journal of Clinical Nutrition 2015.


This was a randomized trial that spanned one year, or 52 weeks total.

A total of 115 obese and overweight adults with type 2 diabetes participated. Their age ranged from 35 to 68 years.

The participants were randomly assigned to one of two diets that contained an equal amount of calories:

  • Low-carb diet (LC): Carbs, protein and fat comprised 14%, 28% and 58% of calories, respectively. The total carb content was under 50 grams per day.
  • High-carb diet (HC): Carbs, protein and fat comprised 53%, 17% and 30% of calories, respectively.

Both diets restricted calories in order to produce weight loss. Calories were restricted by 30%, which amounted to 500–1000 calories, depending on the individual.

The fat content of the diets was mainly unsaturated, with less than 10% of calories from saturated fats.

In addition, all participants had 60-minute, supervised exercise sessions three times per week. These sessions focused on moderate-intensity aerobic and resistance exercise.

Blood samples were taken at the beginning, in the middle (24 weeks), and at the end (52 weeks) of the study.


78 people completed the study, which is 68% of participants.

Due to regular exercise and the reduction of calories, participants in both groups lost weight and achieved significant health improvements.

This graph shows the weight changes in the two groups:


Changes in the following health markers were similar between groups:

  • Weight loss: The LC group lost 9.8 kg (21.6 lbs) and the HC group lost 10.1 kg (22.3 lbs).
  • HbA1c: Levels dropped by 1% in both groups.
  • Fasting blood sugar: Decreased by 0.7 mmol/L (27.02 mg/dL) in the LC group and 1.5 mmol/L (57.9 mg/dL) in the HC group.
  • LDL cholesterol: Levels dropped by 0.1 mmol/L (3.9 mg/dL) in the LC group and 0.2 mmol/L (7.7 mg/dL) in the HC group.
  • Blood pressure: Fell by 7.1 mmHg in the LC group and 5.8 mmHg in the HC group.
  • Inflammation: Estimated by the C-reactive protein, this decreased by 0.9 mg/L in the LC group and 1.2 mg/L in the HC group.
  • Insulin resistance: Also decreased substantially.

However, the low-carb group experienced significantly greater improvements in several health markers.

These included improvements in the following:

  • Medication: Greater reduction in the need for diabetes medication.
  • Glycemic variability: At least twice the decrease in glycemic variability, indicating greater stability in blood sugar levels.
  • Hyperglycemia: Less risk of experiencing high blood sugar levels.
  • Triglycerides: 0.4 mmol/L (7.2 mg/dl) reduction in triglycerides, versus a 0.01 mmol/L (0.18 mg/dl) reduction in the HC group.
  • HDL cholesterol: Increases of 0.1 mmol/L (1.8 mg/dl), versus 0.06 mmol/L (1.08 mg/dl) in the HC group.


For overweight or obese people with type 2 diabetes, calorie-restricted diets and regular exercise lead to weight loss, improved blood sugar control and reduced risk factors for heart disease.

This happens regardless of whether people follow low-carb or high-carb diets.

However, low-carb diets lead to greater improvements in blood sugar control and blood lipid profile than high-carb diets.

Additionally, low-carb diets decrease the need for diabetes medication and help stabilize blood sugar levels.

For this reason, low-carb diets can help effectively manage type 2 diabetes.


This study was well designed, but had a few limitations.

  1. It did not include a control group of participants who did not change their diet, which would have helped isolate the effects of the lifestyle modifications.
  2. The assignment to diets was not blind.
  3. The LC group’s protein intake was much higher. Protein can affect weight loss as well as glycemic control, so this may have impacted the results of the study.
  4. By the end of the study, the LC group had increased their carbohydrate intake to 74 g, and saturated fat accounted for 11% of calories. Calorie intake was increased throughout the study in both groups.
  5. Adherence to the diet was good but not perfect, which is a common limitation of these types of studies.



The main outcome variable of the current study was HbA1c.

HbA1c is also known as glycated hemoglobin. Measuring HbA1c gives clinicians and scientists an idea of the average blood sugar levels over the previous few months.

High HbA1c levels are associated with an increased risk of developing diabetes-related complications.

Some studies have found no significant differences in the effects of low- and high-carb diets on HbA1c. Conversely, other studies have reported greater reductions in HbA1c with LC diets.


Studies that have compared LC diets with calorie-restricted HC diets among patients with type 2 diabetes have provided mixed results.

Some reported that LC diets caused greater weight loss.

In the current study, both diets contained the same amount of calories, and weight loss was similar.

This suggests that the main cause of weight loss is calorie deficit rather than the nutrient composition of the diets. Several previous studies support this.


Supporting the present study, one 24-week randomized controlled trial in obese adults with type 2 diabetes showed that a LC diet caused greater improvements in blood sugar control and blood lipid profile than a HC diet.

Similarly, previous studies have reported greater reductions in triglycerides and higher increases in HDL-cholesterol with LC diets.

In the current study, similar reductions in LDL-cholesterol were seen in both the LC and HC diets.

In contrast, large reviews of previous trials suggest that very LC diets may have less favorable effects on LDL cholesterol than conventional high-carb, low-fat diets.

These differences may be explained by the type of fat replacing carbs in LC diets. In the present study, carbs were replaced with unsaturated fat, which may lower LDL-cholesterol.

Conversely, saturated fats may raise the levels of LDL-cholesterol.


In conclusion, reducing calories and increasing exercise can lead to weight loss and improved health — regardless of whether people are on a low-carb or high-carb diet.

However, for obese people who have type 2 diabetes, a low-carb diet seems to be more effective at improving blood sugar control and reducing the risk factors for heart disease.

This is supported by several studies showing that low-carb diets are effective for diabetics.

Keys Of The Morning Fat Melter Program

Morning Fat Melter


First thing you want to achieve is to transform yourself into a person with a high energy level, so for this to happen the next are really important.

Breathing is really important for our recovery. That’s why, no matter what your job is, you should have a break each 90 to 120 minutes, no matter what.

In that break, simply drink a glass of water or two, have a small snack or a meal, as instructed in the Meal Plan, and breathe this way: Breathe in to a count of 3, and out to a count of 6, to lower arousal and to quiet not just the body, but also the mind and the emotions.

The second source of energy, after the right breathing comes from the foods we eat. That’s why you must follow the Meal Plan we created especially for you.

Because our energy level and our metabolism gets slower during the end of the day, and I want you to burn as much fat as possible in the hours before going to bed and during your sleep, the last 2 meals, are very low in carbs, but filled with protein.

A study done by The University of Minnesota, researchers have compared groups of women on a 1700 calories a day diet. The group that ate the largest percentage of their food earlier in the day, felt less tired and in average lost 2.3 pounds per week more than those who ate most food later in the day, so be sure you follow the meal plan I created for you.

Also drinking water is another source of physical energy removal and a key to making The Morning Fat Melter program a success for you. By the time you feel thirsty is already too late, because your body is already dehydrated. Dehydrate a muscles as little as 3 % and it will lose 10% of its strength and 8% of its speed. So, be sure you drink 3 liters of water per day or more.

Another important part of the program is getting enough sleep. You must sleep around 7-8 hours per day. Less is bad, and more is bad also. Some 50 studies have shown that memory, concentration, performance, metabolism and the ability to lose weight declines steadily as sleep debt increases, so make sure you stay in the 7-8 hours per 24 hours range.

Most of the fat you will lose while on The Morning Fat Melter System will be lost during the deepest levels of sleep; in fact, if you follow our plan precisely, your body will burn fat up to 20 hours a day.

During sleep, cell division is most active, the greatest numbers of growth hormones and repair enzymes are released and muscles that have been stressed during the day have an opportunity to regenerate.

If you had a bad night and couldn’t get enough sleep, simply take a nap in the afternoon. Sleep 30-40 minutes only and you will wake up refreshed.

This is important and will increase performance on the job. NASA’s Fatigue Counter Measures Programs has found that a short nap of forty minutes improved performance by an average of 34 % and alertness by 100 %.

Doing your morning workouts is the best way to have a high energy level throughout the day. Our workouts are the best way to lose weight, increase your energy level and fitness level in a short period of time.

Our workouts also include strength training exercises. On average, we lose nearly ½ pound of muscle per year after the age of 40 in the absence of regular strength training, which means that also our metabolism is getting slower.

More and more physiologists have come to the conclusion that muscle loss, more than any single factor, is responsible for both the frailty and the diminished vitality associated with old age.

However, you will see that our workouts will give your more strength, energy and a big fat loss effect.

Another form of energy that is really important is emotional energy. We have to enjoy life, because otherwise there is no reason to live.

A Study was made at the School Sister of Notre Dame Congregation, on over 700 aging nuns. The study set out to study the factors that differentiate nuns who eventually got Alzheimer’s disease from the ones who did not.

All the nuns included in the study had to write down a personal assay when they joined the congregation. Upon analysis, the study showed that the nuns who were filled with positive emotions in the essay (happiness, love, gratitude, hope, contentment) did not have the disease and have lived almost 20 % longer and had more productive lives compared to the ones who had negative feelings.

So, each time you feel negativity, TRY NOT TO STAY STUCK IN NEGATIVITY. My goal is to help you return your body to it’s normal healthier state as soon as possible.


Discover How Jennifer Lost 43 Pounds of FAT in Just 8 Weeks!

Anathor Story: Discover Jill’s story – She lost 21 pounds in her first month by following my Program.

Positive emotions are the Best Fuel for WEIGHT LOSS!

An activity that is enjoyable, fulfilling and affirming, tends to prompt positive emotions. Depending on your interests that may mean singing, gardening, dancing, making love, doing yoga, reading an absorbing book, playing a sport, visiting a museum, attending a concert or simply spending time alone after an intensive day of engaging with other people. This is really important!

This is the reason why in the Morning Fat Melter program, it is really important to do one of the actions I mentioned above 1-2 times per week.

This way, your emotional reservoir will be filled and you will have enough energy to become the new you!

Studies have shown that watching TV is not good at all. In fact it increases stress, creates anxiety and low-level depression.

In contrast, the richer and deeper the source of emotional recovery, the more we refill our reserves and the more resilient we become. Effective emotional renewal puts us in a position to perform more effectively, especially under stress.

So here are a few actions that you must do in the 30 days of the program in order to be 100 % it will work for you:
– Make a list of 10 things you really enjoy doing.
– Pick the top 2 of them, and do each one of them at least once a week
– Do not watch TV during these 30 days. Try not to….

Don’t forget to share this article about My Morning Fat Melter Program with your friends using the social media icons.

Proof that Ketogenic Diets Increase NAD+ to Curb Inflammation and prevent brain degeneration


Ketogenic diets — extreme low-carbohydrate, high-fat regimens that have long been known to benefit epilepsy and other neurological illnesses — may work by lowering inflammation in the brain, according to new research by UC San Francisco scientists. The UCSF team has discovered a molecular key to the diet’s apparent effects, opening the door for new therapies that could reduce harmful brain inflammation following stroke and brain trauma by mimicking the beneficial effects of an extreme low-carb diet

New research uncovers and replicates the mechanism by which a ketogenic diet curbs brain inflammation. The findings pave the way for a new drug target that could achieve the same benefits of a keto diet without having to actually follow one.

The keto diet is focused on reducing the amount of carbohydrates as much as possible and increasing the amount of protein and fat.

Besides its weight loss-related benefits, recent studies have pointied to many other advantages. For instance, Medical News Today recently covered research suggesting that the diet may increase longevity and improve memory in old age.

Other studies have noted the neurological benefits of the diet. The keto diet is used to treat epilepsy, and some have suggested that it may prove helpful in Alzheimer’s and Parkinson’s disease.

However, the mechanism by which a keto diet may benefit the brain in these illnesses has been a mystery. The new research – which was led by Dr. Raymond Swanson, a professor of neurology at the University of California, San Francisco – suggests that it may do so by reducing brain inflammation.

In the new study, Dr. Swanson and team show the molecular process by which the keto diet reduces brain inflammation. The researchers also identify a key protein that, if blocked, could create the effects of a keto diet.

This means that a drug could be designed to reduce inflammation in patients who cannot follow a keto diet because of other health reasons.

The findings were published in the journal Nature Communications.

A keto state lowers brain inflammation

A keto diet changes the metabolism, or the way in which the body processes energy. In a keto diet, the body is deprived of glucose derived from carbs, so it starts using fat as an alternative source of energy.

In the new study, Dr. Swanson and his colleagues recreated this effect by using a molecule called 2-deoxyglucose (2DG).

The 2DG molecule stopped glucose from metabolizing and created a ketogenic state in rodents with brain inflammation as well as in cell cultures. Levels of inflammation were drastically reduced – almost to healthy levels – as a result.

“We were surprised by the magnitude of our findings,” said Dr. Swanson. “Inflammation is controlled by many different factors, so we were surprised to see such a large effect by manipulating this one factor. It reinforces the powerful effect of diet on inflammation.”

The restricted glucose metabolism lowered the so-called NADH/NAD+ ratio. Dr. Swanson explained to MNT what this ratio refers to, saying, “NAD+ and NADH are naturally occurring molecules in cells that are involved in energy metabolism.”

“Cells convert NAD+ to NADH, as an intermediary step in generating energy from glucose, and thus increase the NADH/NAD+ ratio,” he added.

When this ratio is lowered, the CtBP protein gets activated and attempts to turn off inflammatory genes. As Dr. Swanson told us, “CtBP is a protein that senses the NADH/NAD ratio and regulates gene expression depending on this ratio.”

So, the scientists designed a molecule that stops CtBP from being inactive. This keeps the protein in a constant “watchful” state, blocking inflammatory genes in an imitation of the ketogenic state.

Significance of the findings, future research

Speaking to MNT about the clinical implications of the study, Dr. Swanson said, “Our findings show that it is […] possible to get the anti-inflammatory effect of a ketogenic diet without actually being ketogenic.”

[The keto] diet is difficult to follow […], especially for people who are acutely ill. Our work identifies a potential drug target that can produce the same effect as [the] ketogenic diet.”

“I think the work also increases the scientific legitimacy of the ketogenic diet/inflammation link,” he added.

Dr. Swanson went on to highlight how important it is that the research conducted by he and his team uncovered a causal mechanism rather than simply pointing to an association.

“Most scientists,” he told us, “are reluctant to accept cause-effect relationships between events in the absence of a defined mechanism. Here we have provided a biochemical mechanism by which diet affect inflammatory responses.”

Dr. Swanson also shared with us some directions for future research. “Our work was very focused on brain trauma,” he said, but “next steps will be to expand the list of pro-inflammatory conditions that can be modulated by the CtBP mechanism.”

The findings could apply to other conditions that are characterized by inflammation. In diabetes, for example, the excessive glucose produces an inflammatory response, and the new results could be used to control this dynamic.

“[The] ultimate therapeutic goal would be to generate a [drug] that can act on CtBP to mimic the anti-inflammatory effect of [the] ketogenic diet,” Dr. Swanson concluded.

“It’s a key issue in the field — how to suppress inflammation in brain after injury,” said Raymond Swanson, MD, a professor of neurology at UC San Francisco, chief of the neurology service at the San Francisco Veterans Affairs Medical Center, and senior author of the new study.

In the paper, published online September 22, 2017 in the journal Nature Communications, Swanson and his colleagues found the previously undiscovered mechanism by which a low carbohydrate diet reduces inflammation in the brain. Importantly, the team identified a pivotal protein that links the diet to inflammatory genes, which, if blocked, could mirror the anti-inflammatory effects of ketogenic diets.

“The ketogenic diet is very difficult to follow in everyday life, and particularly when the patient is very sick,” Swanson said. “The idea that we can achieve some of the benefits of a ketogenic diet by this approach is the really exciting thing here.”

Low-Carb Benefits

The high-fat, low-carbohydrate regimen of ketogenic diets changes the way the body uses energy. In response to the shortage of carb-derived sugars such as glucose, the body begins breaking down fat into ketones and ketoacids, which it can use as alternative fuels.

In rodents, ketogenic diets — and caloric restriction, in general — are known to reduce inflammation, improve outcomes after brain injury, and even extend lifespan. These benefits are less well-established in humans, however, in part because of the difficulty in maintaining a ketogenic state.

In addition, despite evidence that ketogenic diets can modulate the inflammatory response in rodents, it has been difficult to tease out the precise molecular nuts and bolts by which these diets influence the immune system.

Intricate Molecular Waltz

In the new study, the researchers used a small molecule called 2-deoxyglucose, or 2DG, to block glucose metabolism and produce a ketogenic state in rats and controlled laboratory cell lines. The team found that 2DG could bring inflammation levels down to almost control levels.

This image shows hippocampal slices.

Immunostaining for Iba1 and iNOS identify activated microglia in mouse hippocampal slice cultures after 24 h incubation with LPS (10 μg/ml) or LPS + 2DG (1 mM) image is credited to Swanson et al./Nature Communications.

“I was most surprised by the magnitude of this effect, because I thought ketogenic diets might help just a little bit,” Swanson said. “But when we got these big effects with 2DG, I thought wow, there’s really something here.”

The team further found that reduced glucose metabolism lowered a key barometer of energy metabolism — the NADH/NAD+ ratio — which in turn activated a protein called CtBP that acts to suppress activity of inflammatory genes.

In a clever experiment, the researchers designed a drug-like peptide molecule that blocks the ability of CtBP to enter its inactive state —essentially forcing the protein to constantly block inflammatory gene activity and mimicking the effect of a ketogenic state.

Peptides, which are small proteins, don’t work well themselves as drugs because they are unstable, expensive, and people make antibodies against them. But other molecules that act the same way as the peptide could provide ketogenic benefits without requiring extreme dietary changes, Swanson said.

The study has applications beyond brain-related inflammation. The presence of excess glucose in people with diabetes, for example, is associated with a pro-inflammatory state that often leads to atherosclerosis, the buildup of fatty plaques that can block key arteries. The new study could provide a way of interfering with the relationship between the extra glucose in patients with diabetes and this inflammatory response.



Best Sulforaphane Supplements for Nrf2 Activation – Containing Glucoraphanin + Myrosinase

For a while now, Sulforaphane has been a hot topic within the scientific community. Its received particular attention from Rhonda Patrick and Tim Ferriss. Whilst it can consumed via broccoli sprouts, these aren’t always easy or convenient to consume. The below post discusses the best supplement options.

Jed Fahey, one of the leading researchers in the field, warns us to be careful of which supplement we use. Saying their lab, which has analyzed dozens of supplements over the years, has found that many are terrible, and don’t contain what they say they do.

To complicate matters, there are 3 main ways to consume sulforaphane:

  1. Pure Sulforaphane – Average bioavailability of 70%*
  2. Glucoraphanin + Myrosinase – Average bioavailability of 35%*
  3. Glucoraphanin – Average bioavailability of 10%*

* Bioavailability numbers come from Jed Fahey’s research at Johns Hopkins. See source #3 below for more info.

Below are a list of the best sulforaphane supplements. All are currently used by Jed Fahey’s team at Johns Hopkins University in their clinical studies:

1. Prostaphane

Consuming active sulforaphane itself has the greatest potential affect (measured using a term called bioavailability). Currently, there is only one free-form stabilized sulphoraphane product on the market. Its name is Prostaphane, and is manufactured in France by a company called Nutrinov.

You may see products advertising that they contain Sulforaphane (specifically Sulforaphane Glucosinolate), however, it should be noted that this is misleading. Whilst it is technically accurate to say that they contain the glucosinolate form of sulforaphane, actually they contain glucoraphanin. It then needs to be converted into sulforaphane via myrosinase.


2. Avmacol

The next best alternative to active sulforaphane is consuming the precursor glucoraphanin alongside the activation enzyme myrosinase.

Avmacol is a high end supplement made by Nutramax Laboratories. It is glucoraphanin extracted from Broccoli seeds, plus the active myrosinase enzyme.

Each Avmacol pack contains 60 tablets, which at 2 tablets per day, is a 1 months supply.


3. Crucera-SGS

Crucera-SGS is a supplement from Thorne Research containing concentrated glucoraphanin.

Crucera-SGS comes in 60 tablet packs, doses at 1 tablet per day, so 2 months supply.

As briefly mentioned above, although the supplement ingredients read “Sulforaphane Glucosinolate”, this isn’t to be confused with active sulforaphane (found in prostaphane). Sulforaphane Glucosinolate is actually Glucoraphanin, before it has been transformed by the enzyme myrosinase, into sulforaphane.

To recap:

  • All 3 supplements mentioned above are currently used in clinical trials by Johns Hopkins University. This means that they’ve been tested and confirmed to contain what they say.
  • The most bioavailable sulforaphane supplement you can buy is called prostaphane, but so far, is only distributed in France.
  • Next most bioavailable (and accessible in the USA) is Avmacol, because it bundles the enzyme myrosinase alongside its glucoraphanin.

Growing & Consuming Fresh Broccoli Sprouts

If you’ve read through the above, you’ll realize there doesn’t exist an optimal supplement. Even if prostaphane were available in the USA, its cost would likely be high.

Whilst supplements are great for busy lifestyles, whilst you’re on the go. If you’ll be staying in one place for a while, a good alternative is to grow broccoli sprouts yourself.

It’s really simple to grow broccoli sprouts, you just need a seed sprouter (Rhonda uses Ball jars + sprouter lids, but any jar + mesh will do), and some organic broccoli sprout seeds. This video gives a good overview on how to produce your own.

The dosage used in clinical trials often ranges from 30-60mg of sulforaphane. Estimates land fresh broccoli sprouts at a concentration of about 1 gram fresh weight to around 0.45mg of sulforaphane. So to achieve 30-60mg, you’d need to consume between 67-134g of sprouts.

Rhonda says (on her latest Tim Ferriss podcast) she consumes up to 4 ounces (113g) of broccoli sprouts a few times per week. Broccoli seeds yield approximately 5:1. So this means if you start off with 1 ounce of broccoli seeds, you’d end up with approximately 5 ounces of sprouts.

To achieve Rhonda’s 8 ounces consumption per week, you need to grow approximately 1 and a 1/2 ounces (43g) of seeds each week. To put a price to that, Todd’s seeds (for example) are $24 per pound (1lb = 16 ounces). So you’re looking at a cost of $2.25 of seeds per week. That’s not very expensive, given the potential long term health benefits.

Granted, if you’re consuming 4 ounces of broccoli sprouts in one sitting, its a lot. You’ll probably want to emulate Rhonda, and blend them in with a smoothie. Her blender of choice (like Joe Rogan) is the Blendtec Classic. But any decent blender will do.

Its worth also taking a look at Rhonda’s video on tripling the bioavailability of sulforaphane your sprouts. Essentially you heat your broccoli sprouts to 70C, hot enough that it disables the epithiospecifier protein, but not too hot that it disables the myrocinase enzyme (responsible for converting the glucoraphanin into sulforaphane). We do this because glucoraphanin can be converted into two forms of sulforaphane (regular sulforaphane, the stuff we want, and sulforaphane nitrile, which does not contain the anti-carcinogenic properties we want). By knocking out the epithiospecifier protein, which is needed for converting glucoraphanin to sulforaphane nitrile, we increase potential conversion to regular sulforaphane (yay!).

She uses a Famili temperature monitor to ensure she gets the water at 70C.

Rhonda’s broccoli sprouting setup. Complete with Ball jars, sprouting lids, regular teapot, famili temperature monitor and blendtec blender.


  1. Chemoprotection Center At Johns Hopkins University FAQ
  2. Jed Fahey Interview on Rhonda Patrick’s Podcast
  3. Further publications from Johns Hopkins University research

P.S. Check out this post on supplements that Rhonda Patrick takes – these can make good additions to sulforaphane.

Reducing Saturated Fat doesn’t matter

For decades, saturated fat has been believed to be harmful. This is claimed to be because saturated fat raises blood levels of cholesterol inside LDL lipoproteins, which is a risk factor for cardiovascular disease (heart disease and strokes).

This is often referred to as the diet-heart hypothesis.

However, several major studies in recent years have challenged the diet-heart hypothesis and failed to find a relationship between saturated fat consumption and cardiovascular disease.


A new study recently came out that looks at the relationship between saturated fat consumption and the risk of cardiovascular disease.

Hooper Lee, et al. Reduction in saturated fat intake for cardiovascular disease.The Cochrane Database of Systematic Reviews, 2015.

This is a systematic review and meta-analysis performed by the Cochrane collaboration, an independent organization of scientists that do objective and highly thorough reviews of randomized controlled trials.

When it comes to the quality of scientific evidence, it really doesn’t get much better than a Cochrane review.


The researchers searched the literature for randomized controlled trials that fulfilled certain criteria.

These included, but were not limited to:

  • There was a control group in each study.
  • The study instructed participants to reduce saturated fat, or replace it with other types of fats.
  • The study lasted for at least 24 months.
  • The study looked at hard end points, such as heart attacks and death.

All in all, 15 randomized controlled trials with over 59,000 participants were included.


There were several interesting findings in the study.


A cardiovascular event can refer to several different things. The study defined a “cardiovascular event” as:

“Combined CVD events. These included data available on any of the following: cardiovascular deaths, cardiovascular morbidity (non-fatal myocardial infarction, angina, stroke, heart failure, peripheral vascular events, atrial fibrillation) and unplanned cardiovascular interventions (coronary artery bypass surgery or angioplasty).”

In the current review, intervention that reduced saturated fat intake led to a 17% reduction in cardiovascular events. The quality of evidence was deemed “moderate.”


All-cause mortality refers to death from any cause, including heart attacks, cancer, accidents and others.

This study showed that reducing saturated fat has no statistically significant effect on total mortality. In other words, you are just as likely to die if you significantly cut back on saturated fat intake.


Cardiovascular mortality implies death caused by either heart attacks or strokes. These are currently the two of the world’s most common causes of premature death.

This study did not find any benefit of reducing saturated fat. In other words, those who reduced their intake of saturated fat were just as likely to die from heart attacks or strokes.


The study almost found a small reduction in fatal heart attack risk by reducing saturated fat. The risk ratio was 0.95, or a 5% reduction in risk.

However, this was not statistically significant.


The study found no reduction in non-fatal heart attacks.


There were no reductions in strokes (bleeding or a blood clot in the brain) in groups who restricted their saturated fat intake.


All in all, the only benefit of reducing saturated fat intake was found in cardiovascular events. There was no statistically significant effect on mortality, death from cardiovascular disease, heart attacks or strokes.

However, when they analyzed the studies further, they found a significant reduction in cardiovascular events only when saturated fat was being replaced with polyunsaturated fats.

In other words, reducing saturated fat had no effect on its own, but replacing it with polyunsaturated fats led to a 27% reduced risk of cardiovascular events (but not death, heart attacks or strokes).

They also found that the people who had the greatest reduction in serum total cholesterol were the most likely to experience a benefit.

This implies that changes in fat intake may be beneficial when they actually lead to a significant improvement in blood lipids.


These were the conclusions of the study:

“The findings of this updated review are suggestive of a small but potentially important reduction in cardiovascular risk on reduction of saturated fat intake. Replacing the energy from saturated fat with polyunsaturated fat appears to be a useful strategy, and replacement with carbohydrate appears less useful, but effects of replacement with monounsaturated fat were unclear due to inclusion of only one small trial.

This effect did not appear to alter by study duration, sex or baseline level of cardiovascular risk. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturated fats. The ideal type of unsaturated fat is unclear.”

Cochrane reviews tend to be very conservative in their conclusions. Even though the data clearly suggests that reducing saturated fat is next to useless, they still claim in their conclusion that this is useful advice.

In this case, the study’s conclusions are not supported by the data.


It is hard to find any limitations to this study. It is just about as good as it gets when it comes to studies on nutrition.

The only major flaw is the misleading conclusion.


The findings of this study are similar to a previous Cochrane review that was done in 2011.

It is also in line with findings from other recent systematic reviews and meta-analyses that did not find a link between saturated fat intake and heart disease.


Despite the strange conclusion of the study authors, the data they derived from their review is another nail in the coffin of the diet-heart hypothesis.

This high-quality study shows that reducing saturated fat has no effect on heart attacks, strokes or the risk of dying from all causes.

However, there may be a modest cardiovascular benefit to replacing saturated fats with polyunsaturated fats, such as those found in fish, nuts and olive oil.

According to this current study, this is unlikely to prolong your life, but it may reduce your risk of experiencing a cardiovascular event slightly.

Importantly, despite saturated fat not being harmful in reasonable amounts, this does not mean that people should go out of their way to eat more of them.

This study only looked at people using reasonable amounts of saturated fat, and does not exonerate bulletproof coffee users – which are using much higher amounts of saturated fat than the participants in this review.


Saturated fats appear to be neither good, nor bad. They are just neutral.

However, we do know that there are fats out there that have actual benefits.

Emphasizing foods that contain healthy fats, such as fish, nuts, seeds and extra virgin olive oil, may lead to a net health benefit.

In other words, don’t avoid saturated fats, but still try to prioritize whole foods that contain fats that have clearly been shown to be healthy.

How the war on Cholesterol caused our diabetes epidemic


Cholesterol is a molecule required by every cell of the body in fairly large amounts. It can be easily synthesised by these cells, or taken up by them from LDL and other ApoB lipoproteins, but cannot be broken down. Cholesterol is not soluble in water, and thus must be carried through the blood on lipoprotein particles. When the cholesterol produced or taken up by the cells of the body becomes surplus to requirements it is extracted by HDL (ApoA1 lipoproteins) and carried back to the liver for disposal as bile salts and acids (most of this cholesterol is reabsorbed and recycled, but there is also a variable amount lost in faeces). Reverse cholesterol transport (RCT) is the term used for this extraction of unneeded cholesterol. Here we describe a simplified version of reverse cholesterol transport, how this has been modified by new research into HDL, and we explain the effect of raising or lowering insulin and insulin sensitivity on RCT.

This video gives a good overview of the systems we’ll be describing. (The brain has its own, largely separate cholesterol system which we’ll ignore for now).

Cholesterol and insulin

We have about 30g of cholesterol in our bodies, and synthesise well over a gram a day. Only 10% of this is synthesised in the liver, and even less if we eat cholesterol or have a reduced requirement. Our requirement goes up when we are growing (cells are expanding and new cells being made) and down when we are fasting or losing weight (when fat cells and glycogen cells are shrinking, and autophagic processes are clearing unwanted cells). Thus it makes sense, and helps to keep cholesterol in balance with requirements, that cholesterol synthesis is stimulated by insulin (the fed state hormone) and inhibited by glucagon (the fasting state hormone).[1] An additional check on cholesterol synthesis in the fasting state is the activation of AMPK by the ketone body B-hydroxybutyrate.[2] No surprises then that cholesterol synthesis is found to be increased in type 2 diabetes.[3]

If scientists want to create the early signs of heart disease in animals, they need to feed them doses of cholesterol much larger than the total capacity of the body to make cholesterol.[4] However, Jerry Stamler, one of the founding fathers of the diet heart hypothesis, found in the early 1960’s that animals treated in this way got better when the cholesterol feeding stopped – unless they were given extra insulin.[5] This vital clue was missed in the later rush to change our diets – Jerry Stamler advised the population to avoid egg yolk and replace fat with refined carbs, yet human diets never supplied the amount of cholesterol he fed his animals – unfortunately, the new, modified human diet would start to increase insulin to the high levels seen in those chickens once the diabesity epidemic got underway.


Reverse Cholesterol Transport

Fortunately our gut and liver cells make a protein called ApoA1, which the liver turns into something called a nascent HDL particle. Unlike VLDL and the other ApoB particles, which are released from the liver as large, fat and cholesterol laden spheres, HDL is produced in an embryonic state, just a few proteins with little if anything in the way of lipids (lipid-poor ApoA1), and only becomes what we call HDL by performing its cholesterol-gathering role out in the body.


If we focus on the cells believed to play the major role in atherosclerosis, macrophages (large immune cells) which can turn into foam cells if they become overloaded with cholesterol, we can see HDL at work. Macrophages clear the blood of infectious agents and damaged particles, and have a particular affinity for oxidised LDL particles (oxLDL).[6] LDL becomes oxidised if it stays in the blood too long (more likely with higher levels or small, dense particles) and is exposed to excessive glucose and fructose levels after meals, or to smoking and other oxidative stressors.[7,8,9] Brown and Goldstein, who won the Nobel Prize for discovering the LDL receptor, estimated that 30-60% of LDL is cleared from circulation by macrophages. (Macrophages exposed to excess insulin increase their uptake of oxLDL by 80%).[10] The oxLDL is then broken down and the cholesterol stored – remember it can’t be broken down. As in other cells, any excess is sent to the surface of the cell, to transporters and other structures that make it available for HDL to pick up, as free cholesterol (cholesterol efflux). If this doesn’t happen for some reason, over a long period, there’s a risk of foam cell formation and atherosclerosis. (Macrophages exposed to excess insulin decrease their efflux of cholesterol to HDL by 25%).[10]

LCAT and esterification

After HDL picks up free cholesterol, this is esterified by an enzyme called lecithin cholesterol acyltransferase (LCAT), making the HDL particle larger. Cholesteryl ester (CE) is cholesterol joined to a fatty acid, usually an unsaturated fatty acid, which is supplied from the phospholipids also picked up from cells by HDL. The more effectively HDL can esterify cholesterol, the sooner it can return to pick up more from the macrophage (or other cell) – this is called HDL efflux capacity – and the phospholipids found in egg yolk have been shown to increase HDL efflux capacity.[11] Phospholipids, found in all whole foods, especially fatty ones like eggs, nuts, seeds, liver, shellfish, and soya beans, are good things to have in your diet; you won’t get them from eating flour, sugar, and oil.


Cholesteryl oleate – a cholesteryl ester


CETP – swapping cholesteryl esters for triglycerides

HDL renews itself in the bloodstream by moving cholesteryl esters onto VLDL and other ApoB particles, in more-or-less equal exchange for triglycerides (TGs), through a banana-shaped protein tunnel called Cholesteryl Ester Transport Protein (CETP) which docks between ApoA1 and ApoB particles. HDL can then shed the TGs picked up to help feed cells along its path (as ApoB particles also do), turning them into free fatty acids and glycerol by the action of lipase enzymes. However, the CETP exchange is another place where things can go wrong. If there are too many TGs on VLDL, and too many TG-rich VLDL particles, and fats are not being burned by the body (yes, we’re talking about insulin resistance again), then the piling of TGs onto HDL via CETP will result in its recall to the liver after limited efflux.[12] Carrying lots of TGs back to the liver that made them is not a good use of HDL’s time. And the cholesterol esters being transferred to former TG-rich VLDL is what makes the “Pattern B” lipoproteins, small dense LDL, which are more likely to oxidise and more easily taken up by macrophages. LDL really, once it’s done its job of delivering fat, cholesterol, antioxidants and proteins to cells that need them, ought to be helping in reverse cholesterol transport by ferrying the extra cholesterol esters it received from HDL back to the liver. Large, cholesterol-dense LDL particles – “Pattern A” – are better at this. Small, dense LDL particles aren’t taken up as avidly by the liver, so tend to stay in circulation and oxidize. Hence the TG/HDL ratio is a critical predictor of cardiovascular risk, whether or not we factor in LDL.

The exchange via CETP action is thought responsible for the inverse relationship between levels of TG and HDL-C. Specifically, the larger the VLDL pool (higher TG level), the greater the CETP-mediated transfer of CE from HDL to VLDL in exchange for TG, resulting in TG-rich small, dense HDL which are catabolized more rapidly, leading to low levels of HDL-C. These small, dense HDL also have reduced antioxidant and anti-inflammatory properties. Thus, the greater the increase in hepatic VLDL-TG synthesis and secretion that characterizes insulin-resistant/hyperinsulinemic individuals, the lower will be the HDL-C concentration.[12]


Insulin LDL

Insulin resistance in this population (n=103,000) was stratified by tertiles of TG and HDL, with the insulin sensitive tertile having a mean TG/HDL ratio of 1.1 [13]

Fasting, weight loss, and LDL

People who are naturally lean and active and have good insulin sensitivity are at very low risk of cardiovascular disease; they tend to burn fat and have low TG/HDL ratios on any diet. Paradoxically, LDL rises sharply when such people fast for long periods.[14] Despite this, no-one as far as we know has ever suggested that not eating enough causes atherosclerosis. Of course TGs and insulin also fall, while HDL stays the same. But strangely, this rise in LDL does not happen in obese people or people with atherosclerosis.[15]


Fasting LDL Apo B

In healthy lean individuals, LDL and ApoB rise as Insulin-like growth factor falls during a fast.[14]

Fasting Chol athero

In obesity or T2DM, or in this case a patient with arteriosclerosis, cholesterol and LDL do not rise during a fast.[15]

Phinney and colleagues found that LDL first fell, then rose significantly, during major weight loss. They calculated that this was due to the delayed removal of around 100g extra cholesterol from the adipose of obese people. LDL became normal when a weight maintenance diet replaced the (low fat, reduced calorie) weight loss diet.[16]
Think about this – all of this extra 100g of cholesterol, 3x the usual whole body content, was eventually removed by reverse cholesterol transport. Some of it ended up on LDL, increasing the LDL count to the level where statins would be indicated according to guidelines. This did not prevent its removal. There is no “LDL gradient” that forces cholesterol back into the body. The LDL level doesn’t tell you whether cholesterol is coming or going – the TG/HDL ratio is the best guide to that.[17]


Hepatic lipase – burning fat.

ApoA1 and HDL production increases the release of hepatic lipase, so in a sense ApoA1 is a fat-burning protein, which helps to explain why eating fat increases ApoA1 output.[18, 19] More lipase means lower TGs all round. So, making more HDL can lower TGs, just as making too many TGs can lower HDL – but only the latter is likely to be harmful.

Of course, a low fat, high carbohydrate diet decreases ApoA1, but this doesn’t mean it’s bad if you’re insulin sensitive and have low TGs (and low LDL) eating such a diet, as many people do; the lower lipid circulation all round probably just means that less ApoA1 will be required for equilibrium. However, the old assumption that the lower fat higher carb diet is the “Prudent” diet hasn’t aged well.

We have previously reported that apoA-I and HDL directly affect HL-mediated triacylglycerol hydrolysis, and showed that the rate of triacylglycerol hydrolysis is regulated by the amount of HDL in plasma.

The antioxidant and antiinflammatory benefits of HDL.

Reverse cholesterol transport is the core business of HDL, but it isn’t the only business; HDL is like a busy doctor with a useful bag of healing tricks trundling up and down your bloodstream. For example, HDL carries an antioxidant protein, PON1. When a fatty hamburger meal rich in lipid peroxides was fed to 71 subjects, those with higher HDL experienced a much smaller rise in oxLDL.[20]

The pre-meal HDL level was associated with the extent of the postprandial rise in oxidized LDL lipids. From baseline to 6 h after the meal, the concentration of ox-LDL increased by 48, 31, 24, and 16 % in the HDL subgroup 1, 2, 3, and 4, respectively, and the increase was higher in subgroup 1 compared to subgroup 3 (p = 0.028) and subgroup 4 (p = 0.0081), respectively. The pre-meal HDL correlated with both the amount and the rate of increase of oxidized LDL lipids. Results of the present study show that HDL is associated with the postprandial appearance of lipid peroxides in LDL. It is therefore likely that the sequestration and transport of atherogenic lipid peroxides is another significant mechanism contributing to cardioprotection by HDL.

Tregs or T regulatory cells are a type of immune cell that switches off inflammatory responses. They are also a type of cell that takes up HDL, and HDL selectively promotes their survival. This is a good thing.[21]

Can LDL help in reverse cholesterol transport?


The answer is yes – if it’s large LDL particles (Pattern A), not so much small dense ones. Triglycerides and VLDL, on the other hand, are no help at all.

There are two pathways by which RCT can occur. In the first, the scavenger receptor class B type 1 (SRB-1) mediates hepatic uptake of CE from HDL particles without uptake of apoA-I or the whole HDL particle [74]. In the second pathway, cholesteryl ester transfer protein (CETP) catalyzes the transfer of CE from HDL to apoB-containing lipoproteins (VLDL and LDL) in exchange for TG from the apoB-containing lipoproteins (Fig. 1) [21, 75]. This exchange results in apoB-containing lipoproteins which are enriched with CEs and depleted of TGs, and HDL particles which are depleted of CEs and enriched with TGs. The TG-rich and CE-poor HDL particles are catabolized faster than large, CE-rich HDL (apoA-I FCR is increased as noted in Fig. 1), a finding resulting in lower levels of HDL-C in the setting of high TG levels [76]. The apoB-containing lipoproteins, now enriched in CE, can also be taken up by the liver receptors as previously described [75]. When TG levels are high, the apoB particles are TG-enriched and hepatic lipase then hydrolyzes the TGs within the TG-rich LDL to release FFAs, a process which remodels the LDL particles into smaller and denser LDL particles which can enter the arterial intima more easily than larger LDL particles, thus making them more atherogenic (Fig. 1). Small, dense LDL particles also bind less avidly to the LDL receptor, thus prolonging their half-life in the circulation and making these particles more susceptible to oxidative modification and to subsequent uptake by the macrophage scavenger receptors [12].

An unusual experiment (using a radioactive nanoemulsion mimetic of LDL) showed that LDL cholesterol is removed from circulation more rapidly in resistance-trained healthy men than in sedentary healthy men. oxLDL was 50% lower in the resistance-trained men – but total LDL levels were the same, probably as a result of increased beta-oxidation (fat burning).[22]

Why are doctors being confused about HDL and reverse cholesterol transport?

There’s a trend in mainstream medicine to be dismissive of HDL and treat reverse cholesterol transport as unimportant; LDL lowering is the thing. New evidence from genetics, epidemiology, and drug trials is increasingly misinterpreted in this way – probably because drugs that increase HDL have, with some exceptions, been failures. However, drugs that raise HDL, and lower LDL, by inhibiting CETP are not helping either particle do its job; so far, they have neither decreased nor increased the rate of heart attacks in people taking them. Drugs that raise HDL by increasing ApoA1 and nascent HDL output, like the fibrates (e.g. gemfibrozil), do decrease CHD – but only in people with lower HDL and higher TGs! Moderate alcohol use, which also increases ApoA1 output, seems to have a similar effect, though the first randomised controlled trial of this observational hypothesis is only beginning.[23, 24] Even statins help with RCT by decreasing the synthesis of cholesterol in peripheral tissues, thus leaving more room on HDL for efflux cholesterol – again, statins only seem to reduce CHD in the subgroup of people with lower HDL. Clearly reverse cholesterol transport is very important, and efficient reverse cholesterol transport can best explain why so many people with high LDL and high cholesterol do enjoy long lives free from cardiovascular disease. Some ApoA1 genes that especially promote RCT are associated with reduced CVD risk, notably ApoA1 milano – which is actually associated with low HDL, because HDL clearance is so rapid – a paradox which highlights the trickiness of measuring a dynamic process across all tissues only by what appears in the blood.[25] Efficient RCT is associated with lean genes, but it’s largely something you have to work for – eating right, exercising, and looking after yourself in various ways – including giving up smoking, or not starting – which may be why the drug industry has largely given up on it.[26]

We observed that normolipidemic smokers present higher total plasma and HDL phospholipids (PL) (P < .05), 30% lower postheparin hepatic lipase (HL) activity (P < .01), and 40% lower phospholipid transfer protein (PLTP) activity (P < .01), as compared with nonsmokers. The plasma cholesteryl ester transfer protein (CETP) mass was 17% higher in smokers as compared with controls (P < .05), but the endogenous CETP activity corrected for plasma triglycerides (TG) was in fact 57% lower in smokers than in controls (P < .01). Lipid transfer inhibitor protein activity was also similar in both groups. In conclusion, the habit of smoking induces a severe impairment of many steps of the RCT system even in the absence of overt dyslipidemia.

The latest study on very, very high HDL – why isn’t it good?

Last year we wrote about the CANHEART study, which seemed to show adverse health effects of higher HDL. We wrote then that this was probably showing an effect of alcoholism, hereditary CETP defects, and other factors, and not an increase in heart disease. A new study allows us to look at this problem in more detail.[27]

When compared with the groups with the lowest risk, the multifactorially adjusted hazard ratios for all-cause mortality were 1.36 (95% CI: 1.09–1.70) for men with HDL cholesterol of 2.5–2.99 mmol/L (97–115 mg/dL) and 2.06 (1.44–2.95) for men with HDL cholesterol ≥3.0 mmol/L (116 mg/dL). For women, corresponding hazard ratios were 1.10 (0.83–1.46) for HDL cholesterol of 3.0–3.49 mmol/L (116–134 mg/dL) and 1.68 (1.09–2.58) for HDL cholesterol ≥3.5 mmol/L (135 mg/dL).

Those are some very high HDL levels, and not surprisingly fewer than 4% of men and even fewer women had HDL levels so high that they were associated with any extra risk.
Compare that with 40% of both men and women having low HDL levels that were associated with an equally elevated risk!
Further, the risk associated with very high HDL, though it does include cardiovascular deaths, doesn’t seem to include much increased risk of heart attacks and strokes.


This is consistent with alcoholism (a confounder not measurable with accuracy, as we described in the CANHEART analysis) increasing deaths from heart failure, cancer, and other causes, and with no further benefit (but maybe not much harm overall) from CETP variants elevating HDL.[28] Furthermore, interactions between heavy alcohol consumption and genes associated with higher HDL have been noted in some populations.[29]
Note that the HDL level associated with lowest heart disease and stroke incidence in this study is well to the right of the bell curve of population HDL distribution. Most of these people could have done with more HDL.
Madsen et al discuss their results soberly; although they fail to discuss the potential role of alcohol, which would explain the exact pattern of increased mortality seen well, and don’t highlight the 10-fold larger impact associated with low HDL in their study, there is nothing biased about their analysis. The European Heart Journal’s editorial was also worth reading.[30]


However, as reported in medical media, the message changed a bit.

“It appears that we need to remove the focus from HDL as an important health indicator in research, at hospitals and at the general practitioner. These are the smallest lipoproteins in the blood, and perhaps we ought to examine some of the larger ones instead. For example, looking at blood levels of triglyceride and LDL, the ‘bad’ cholesterol, are probably better health indicators,” he notes.

Well yes, looking at everything is good, and TGs and the TG/HDL ratio as well as LDL will give you extra information about the likely reasons for low HDL and whether you need to worry about it. However, Denmark, where the extremely high HDL study was done, is a place where high LDL (the ‘bad’ cholesterol, remember) is associated with lower all-cause mortality in those over 50 free from diabetes or CVD at the start of the study.[31] Over 50 is when most CVD and type 2 diabetes is diagnosed, so LDL might not be all that informative unless you can look at the subclasses of oxLDL, sdLDL, particle number, and so on (of course part of the effect of LDL in Denmark will be due to that country’s higher dairy fat intake, which will also raise HDL and LDL particle size, maybe helping to explain why the association is so favourable in that population).

If we look at the PURE study, higher fat consumption is associated with both higher LDL and higher ApoA1 and HDL, with saturated fat (like all fat types) tending to improve the ApoB/ApoA1 ratio.[32] This is consistent with many other lines of evidence.

Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all ptrend<0·0001).

This is just what fat-burning does, and there’s maybe not a lot of reason to think it’s good or bad per se. What is good about it is, that fat burning lowers insulin. Insulin is what makes your cells hoard cholesterol, and it’s also one of the things that can mess with reverse cholesterol transport. If you’re making or using excess insulin, the switch to a fat burning metabolism allows the insulin to normalise and causes your cells, including the macrophages, to let go of cholesterol – and when they do, the lipoproteins are there ready to carry it away.


Reverse cholesterol transport manages cholesterol flux through all cells and helps us reach a healthy old age.

LDL cholesterol is not a reliable guide to the state of cholesterol flux unless TG/HDL (and HbA1c) are factored in as well. LDL may increase when cholesterol is being removed or in states where it is not being taken up by cells.

Reverse cholesterol transport can remove prodigious amounts of cholesterol from the body during weight loss.

Excessive triglycerides due to insulin resistance can impair reverse cholesterol transport, as can smoking.

Various nutritional factors found in whole food diets have been found to assist in reverse cholesterol transport (including phospholipids, CLA, and polyphenols).

HDL in the high (if not the “extremely high”) range usually correlates with efficient reverse cholesterol transport and has benefits for cardiovascular health, inflammation, antioxidant status etc, but people with HDL outside (higher or lower than) the ideal range can be equally healthy if their overall metabolic health (insulin sensitivity) is good.

The TG/HDL ratio is a good measure of insulin sensitivity, and if excessive can be improved by lowering excessive insulin levels. A low carb diet, intermittent fasting, exercise, or weight loss are all effective ways to correct the TG/HDL ratio.



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Lancet Diabetes Endocrinol 2017 Published Online August 29, 2017
PURE lipids and BP