Glucose Ketone Index (GKI) – What Ratio Do I need for Nutritional Ketosis Benefits?

Generally these blog posts are a result of scratching my own itch (answering my own question), and this post is no different.

At the time of writing this, I’m doing a 5-day fast, and wanted to understand the readings I’m getting for my blood glucose and blood ketone levels.

Initially I thought that blood ketones were all that mattered, and certainly a lot of people only talk about that reading. But looking at Dr Thomas Seyfried’s paper on treating brain cancer (glioblastomas).  It suggests that its important to take into account blood glucose also. In their study, they acheieved optimal results when their patients maintained what they called ‘nutritional ketosis’. And as part of the paper, they included a formula for what this means.

The chart below describes visually what they mean by nutritional ketosis, and how it affected the tumour growth. The red is an increase in ketones as a fictional patient goes deeper into ketosis. The black line represents blood glucose, that decreases to a plateau, as carbohydrate sources are removed from the diet, and glycogen stores decrease.

So that sweet spot they reach at the end is an optimum level of nutritional ketosis. Now… obviously in our case we are (hopefully) not trying to slow the growth of a glioblastoma. But by getting into ketosis we’re hoping to achieve a number of benefits including:

  • Reduced IGF-1
  • Immune system rejuvenation (perhaps mainly lymphocytes)
  • Increased cellular autophagy
  • Reduced inflammation (often measured by improved C-reactive protein levels)

The extent of these benefits will depend if you’re eating a keto diet, or doing a water fast/fast mimicking diet. But all 3 should improve the biomarkers such that you have a reduced risk of major diseases such as diabetes, cancer and cardiovascular disease.

And studies like this one indicate that the optimal benefits from ketosis lie in maintaining  a 1:1 or lower ratio of glucose to ketones.

So on to the crux of this post, how to calculate GKI. What you’re trying to do is compare apples with apples, you really really want both readings in mmol/L. In my case, having a meter sourced from the UK, that’s how they came, so I simply do:

Glucose Reading (mmol/L) ÷ Ketone Reading (mmol/L)

However, if you’re in the USA, your blood glucose reading will be in mg/dL. You’ll know, because the meter should say mg/dL. But to be sure, if you blood glucose is in the 100s as a score, rather than single digits, that’s likely mg/dL.

So you’ll want to convert that glucose reading into mmol/L by doing:

Your Glucose Reading (mg/dL) ÷ 18.02

This converts your reading from mg/dL into mmol/L, and then you can do the above calculation (glucose reading divided by ketone reading) to get your glucose ketone index score.

So that’s it really, pretty simple.

Links that may be of use:

1 – Thomas Seyfried et al’s paper on using the glucose ketone index to treat brain cancer:
The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer

2 – An excel calculator for the GKI, developed by Dr Seyfried’s colleague Joshua Meidenbauer:
Glucose Ketone Index Calculator

What sticks out for me with all this stuff, is how amazingly valuable it can be in our treatment (and prevention of cancer), and yet in 2017 an incredibly small number of people (& physicians!) know and understand this work. For those with cancer, if its combined with other treatments (described by Dom D’Agostino here), its even better. Its 5 years since Thomas Seyfried published his book ‘Cancer as a Metabolic Disease’. Time will tell how fast we are able to communicate this “meme” to a wider audience.

Rhonda Patrick’s Diet in Detail – Breakfast, Lunch & Dinner

Rhonda Patrick talked recently on the Tim Ferriss podcast about her diet. She described a number of her main meals:

Breakfast Variation #1:

  • Scrambled egg topped with tomatillo salsa (for flavour)
  • Satueed Kale + Garlic topped with olive oil, salt and mustard powder
  • Grapefruit
  • Avocado oil, for cooking the eggs and kale in

Breakfast Variation #2

  • Nut & Berry Cereal – including walnut, pecan and macademia nuts + blueberries
  • Hydrolyzed collagen powder – from
  • Coconut milk
  • Flaxseed
  • Occasionally she adds almond butter, yogurt or VSL #3

Lunch #1 – Smoothie:

Smoothie  v1 (also see her YouTube video on making version 1):

  • 8 large kale leaves
  • 4-6 rainbow chard leaves with stems
  • 3 cups (~710 ml) of baby spinach
  • 2 medium to large carrots
  • 1 tomato
  • 1 large avocado
  • 1 banana
  • 1 apple
  • 1 cup (~710ml) of blueberries (fresh or frozen)
  • 1 tall shot glass of flaxseed (optional)
  • 3 cups (~710 ml) of unsweetened flax milk

N.B. Rhonda drinks about 1/2 of the above in a single serving.

Smoothie v2 (also see her YouTube video on making version 2):

  • Kale (8 leaves)
  • Chard (two rainbow chard leaves and stems)
  • Spinach (2 cups)
  • Celery (2)
  • Parsley (8 pieces)
  • Carrot (1 large)
  • Tomato (1)
  • Apple (1)
  • Lemon (1)
  • Frozen organic blueberries (1-2 cups)
  • Avocado (1)
  • Hydrolyzed collagen powder (1/4 cup)
  • Water (2 cups of water)

Lunch #2:

Dinner #1:

  • Cooked vegetables, including sautéed spinach
  • For protein, often baked wild alaskan salmon or occasionally grass-fed fillet steak

 

Dinner #2

  • Large salad full of greens
  • Again, for protein, often baked wild alaskan salmon or occasionally grass-fed fillet steak

Dinner #3

  • Chicken bone soup, with vegetables and spices

Rhonda’s Motivations for Diet Choices

Breakfast #1 – Scrambled Eggs with Kale & Garlic + 1/2 Grapefruit

Eggs

She eats these for the choline they provide. Choline can be converted by the body into acetylcholine, which is an essential neurotransmitter.

Sauteed Kale & Garlic

One reason Rhonda chooses Kale is due to its high concentration of lutein and zeaxanthin. These cartenoids help protect the eyes from damaging blue light. They also beneficial to the brain, improving neural processing and neural efficiency.

Tomatillo Salsa

Rhonda primarily eats her eggs with tomatillo salsa to make them less boring (lol). It’s also high in tomatidine, which has been shown to boost muscle mass in mice by reducing the activity of a gene called ATF4, known for inhibiting muscle protein synthesis.

Grapefruit

The grapefruit provides ferulic acid, a molecule that inhibits the proinflammatory cytokine TNF-alpha and E2 series prostaglandins (which can also be inflammatory). Ferulic acid has also been shown to be anti-carcinogenic. The grapefruit is also a source of naringenin has a variety of potential benefits.

Avocado Oil

Rhonda stays away from cooking oils that are high in polyunsaturated fat, because it is easily oxydized, and consuming oxydized fat is very harmful. Avocado oil is high in monounsaturated, and low in polyunsaturated fat. It has a very high smoke point, meaning that it withstand some heat.

Mustard Powder

She adds mustard powder the kale and other cruciferous vegetables she cooks. This helps convert the glucosinolate in the plants, into isothiocynates. This compound (isothiocynates) has benefits in humans, but interestingly, is toxic to bugs and insects. The plants use it to help prevent being eaten.

Breakfast #2 – Nut & Berry Cereal

Another breakfast Rhonda has is a nut and berry cereal. For the base she combines chopped nuts and a mix of berries with some coconut milk. In addition to the base, she may add hydrolysed collagen powder, flaxseed, raw cacao nibs, almond butter and occasionally VSL#3 (her probiotic supplement of choice).

Chopped Nuts

The cereal contains a wide array of chopped nuts including walnuts, pecan and macadamia nuts.

This provides magnesium, calcium, zinc and omega-3 fatty ALA (although not a substitute for marine omega-3s​).

Berries

Amongst the berries Rhonda adds are blueberries. These are rich in Pterostilbene which is similar to Resveratrol but is 4x more bioavailable. In mice it has been shown to improve brain function, prevent heart disease, and to ward off some types of cancer. They are also rich in anthocyanins, a molecule that has been shown to lower DNA damage. DNA damage has been shown to cause cancer and lead to depletion of stem cell pools + it also plays a role in the aging process.

Rhonda also adds some pomegranate into the cereal. One of the compounds in pomegranate is transformed by gut microbes into a molecule called urolithin A, which causes mitophagy a process important for the renewal of mitochondria. Urolithin A has shown some impressive things in research on other organisms, including improving muscle function and endurance by up to 42% in mice and increasing lifespan by more than 45% in worms.

Hydrolyzed collagen powder

Rhonda eats hydrolyzed collagen for the proline which accelerates wound healing and for glycine which is an important inhibitory neurotransmitter. Great Lakes Hydrolyzed Collagen powder is her brand of choice.

Coconut milk

Coconut milk is rich in medium chain triglycerides. She doesn’t consume dairy milk because it contains salivary protein which binds to Anthocyanin and polyphenols, limiting their bioavailability.

Flaxseed

Flaxseed provide extra alpha lipoic acid and fibre.

Raw Cacao Nibs

Raw cacao nibs have a number of polyphenols including EGCG which activate many antioxidant genes and has been shown to kill cancer cells.

Almond Butter

The almond butter helps to add some flavour and protein

VSL#3

Rhonda adds VSL#3 to replenish her gut microbiome. She opts for the VSL#3 in sachets (as opposed to pills), which contain 450 billion active probiotic cells per serving.

Lunch #1 – Smoothies

Rhonda rotates between a variety of smoothie recipes (example ingredients listed above). The base to most of her smoothies are kale, chard, spinach and avocado. For smoothie #1 listed above, you can check this youtube video and for smoothie #2 above, this youtube video.

Lunch #2 – Avocado with salmon roe and sauerkraut

Avocados are high in potassium and provide all of the various forms of vitamin E (both tocopherols and tocotrienols). Which is good, because if you supplement vitamin E you only get one form of it. They are also a great source of monounsaturated fat.

Salmon roe caviar is a staple of Rhonda’s diet. She particularly likes it because the omega-3 fats are in phospholipid form which has greater bioavailability to be transported into the brain via the mfsd2a transporter. This is the form that is best taken up by the brain (including the developing fetal brain). It also has a good amount of astaxanthin which protects the omega-3’s from oxidation and does the same for neurons. Studies looking at DHA and EPA levels in red blood cells have shown a correlation between higher omega-3 status and having a to 2 cm larger brain volume. So getting omega-3 into and keeping it in the brain is definitely a brain aging priority for Rhonda.

If you’re curious how Rhonda affords to make something like caviar a staple of the diet – its in part due to her buying in bulk. Rhonda buys from a supplier called Vital Choice who offer it in 2.2lbs batches (source: Rhonda talking salmon roe on Instagram).

Sauerkraut is a good source of fermentable fiber aka prebiotics that is fuel for the commensal gut bacteria so that they can produce compounds (such as short chain fatty acids) that feed more commensal bacteria and feed gut epithelial cells which are required to make the gut barrier. These compounds produced by the gut bacteria serve as signaling molecules to make specific types of immune cells, an important indirect role that fiber also has in the diet that helps it influence immune activities. The sauerkraut itself contains various probiotics (mostly the lactobacillus strains) which are beneficial lactic acid producing bacteria which have recently been suggested to possibly play a role in cancer prevention.

Dinner #1 – Cooked Vegetables & Baked Wild Alaskan Salmon

Rhonda likes a range of cooked vegetables, with a particular focus on the cruciferous family, such as:

  • Spinach
  • Collard greens
  • Bok choy
  • Broccoli
  • Brussels sprouts
  • Parsnips

Cruciferous vegetables contain isothiocyanates, and so because of this, she typically eats them with mustard powder sprinkled on top to increase the amount of myrocinase available. Associative studies have shown that the top 20% of consumers of cruciferous vegetable have a 22% reduction in all-cause mortality. For more info on why adding myrocinase to isothiocynates is useful, see this post on sulforaphane – which is a super useful compound which activates the NRF-2 pathway, responsible for regulating around 200 different genes.

Folate in Green Vegetables

Cooked vegetables like sauteed spinach are very high in folate. Folate provides a precursor that makes a DNA nucleotide called thymine. Every time you repair a damaged cell or make a new cell in your liver, muscle, brain etc., you need to make new DNA which means you need folate. Folate was also very recently shown to increase the growth of stem cells, which is important because stem cell pools deplete with age and are a major cause of organ aging and dysfunction. Folate has recently been shown to play a role in protecting telomeres, the tiny caps on the ends of chromosomes that are a biomarker for age because they get shorter every year.

A recent study showed that mothers with highest folate levels had newborns with telomeres 10% longer and every 10 ng/ml increase in serum folate levels, newborns had a 5.8% increase in telomere length which actually suggests that maternal nutrition may actually play a role in determining the length of telomeres that we have to start with.

Wild Alaskan Salmon

Rhonda eats salmon 2-3 times per week, which is what the American Heart Association recommends. They recommend that adults consume 500 mg/d of EPA and DHA (~2-3 servings of fatty fish per wk or ~8 oz of fish/wk). However, the mean intake in Western society is ~135 mg/d and about ~2 servings of fish per month.

EPA is a powerful anti-inflammatory fatty acid that has been shown to lower brain inflammation. DHA is a critical component of all cell membranes that makes up 30% of the fatty acids in the brain, or about 8% of the total weight. Omega-3 fatty acids have recently been shown to positively change gene expression in several brain regions and also generally shown to stave off brain aging. But also important is just not dying. People with the highest omega-3 fatty acid intake have been associated with having a 9% reduced risk of all-cause mortality. For each 1% increment of omega-3 fatty acids in the blood there was associated a 20% decrease in risk of all-cause mortality.

Dinner #2 – Large Salad & Grass Fed Filet Steak

When Rhonda isn’t eating cooked vegetables with her dinner, she’s having a large salad full of greens. These provide her with a range of micronutrients including folate, magnesium, calcium, vitamin K1, lutein, zeaxanthin and sulfoquinovose, a prebiotic that feeds beneficial bacteria in the gut.

Rhonda eats a grass-fed filet steak a few times per month which is a good source of vitamin b12, iron, and zinc. ~16% of all menstruating women are actually iron deficient. For vegetarians it has been recommended to take in about twice the RDA for iron, since iron which is bound to phytate in plant sources is ~2-times less bioavailable

Dinner #3 – Chicken Bone Soup with Vegetables & Spices

Another protein Rhonda rotates for dinner is chicken legs from pasture-raised chicken. In addition to the protein they also provide some cartilage which is high in collagen, proline and glycine.

Occasionally Rhonda takes the chicken bones, and throws them in some water with some spices and vegetables to make a chicken bone soup. This provides all the same benefits as the hydrolyzed collagen powder. Chicken is also very high in selenium which is a cofactor needed for all glutathione-related enzymes to work and also has a modest amount of zinc, copper, and iron.

If you enjoyed this post, you may also enjoy:

  • Dr Rhonda Patrick’s Preferred Supplement List (article link)
  • Rhonda Patrick’s Pregnancy + Baby Product Recommendations (article link)
  • Best Sulforaphane Supplements for Nrf2 Activation – Containing Glucoraphanin + Myrosinase (article link)
  • Tim Ferriss’ Preferred Nootropic Choices (article link)

Tim Ferriss Nootropics Brand Recommendations

Firstly, I’ll give a quick overview of Tim Ferriss nootropics choices. Then later in this post, I’ll go into details on each one.

Tim’s nootropic list:

Tim has tried the majority of smart drugs on the market, including things like the racitam family (piracetam, aniracetam etc), modafinil, ritalin etc. At one stage, before he was a bestselling author, he ran a supplement company called BrainQuicken, focused on selling cognitive enhancement supplements. So he knows his stuff.

As of Sept 2016, Tim has decided the short term gain from many of the popular smart drugs are not worth the long term side effects.

Therefore, Tim Ferriss nootropic choices are a little different from most. That being said, he still uses a number of products that give him a sustainable cognitive boost.

Creatine & Ubiquinol

Tim considers this combination for those with alzheimer’s or other mitochondrial based neurodegenerative diseases in their family history. He takes them on a daily basis.

Lion’s Maine Extract

Tim consumes Lion’s Mane as a drink combined with chaga (another mushroom) and coffee. Known as Four Sigmatic Mushroom Coffee.

Tim alternates between the coffee version (above) and this non-coffee version. One way to consume the mix without coffee is to do as Dr Rhonda Patrick does, and blend it into a smoothie.

Yerba Mate

Tim’s go to brand of Yerba Mate is Cruz de Malta. He also uses the brands Jesper Traditional Yerba Mate and Anna Park.

Exogenous Ketones

Tim recommends two different forms of exogenous ketones; KetoCaNa and KetoForce.

The KetoCaNa is the weaker of the two, but is the most palatable. KetoForce would have a greater impact on your blood ketone level (beta-hydroxybutyrate). KetoForce is an alkaline liquid, that you can add to water to drink. To balance out the alkalinity you can add some lemon juice.

      

For more info on these nootropics, check out the 9 minute YouTube video Tim made on the subject.

If you enjoyed this post, you may also enjoy:

  • Tim Ferriss – 3 Day Fast Protocol Details – Get into Ketosis Quicker and Easier (article link)
  • Dr Rhonda Patrick’s Preferred Supplement List (article link)
  • Rhonda Patrick’s Diet Details – Breakfast, Lunch & Dinner (article link)
  • Rhonda Patrick’s Pregnancy + Baby Product Recommendations (article link)

Tim Ferriss Sardines Brand Choice

If you’ve been paying attention to Tim recently, you’ll know he’s heavily on the band wagon of low carbohydrate, high fat eating. Whether he’s in ketosis, or just maintaining LCHF.

His tinned sardines of choice are Wild Planet Canned Sardines in Olive Oil. These were a recommendations from his good friend, and biochemistry beast Dom D’Agostino. Who himself maintains a largely ketogenic diet.

Wild Planet tout their sardines as sustainably harvested in well-managed fisheries with negligible by-catch or habitat damage. Given the Tim Ferriss affect, and the amount of sardines they must have sold when he recommended them, sustainably harvested is important.

Front of Packaging.

Back of Packaging.

You can see from the back of the packet (above), that the micronutrient content is good. And if we look at the nutritional information (below), we can see the macros are good too. Each tin has 22g fat, 25g protein and 0g of carbohydrate. Ideal for those adhering to LCHF or Keto diets.

Personally I like them in the 12 pack (cheaper in bulk at $28), but they are also available in a 6 pack (at $19).

Generally speaking, I’ll eat these straight out the tin, or if I’m feeling extravagant, spread them on toast and lightly grill with some vinegar, salt and pepper. But here’s another good suggestions for consuming sardines (via the RooshV forum):

Sardine Spread:

  • Take one can (~100g) of sardines in olive oil, remove tail and bones, put them all in a bowl
  • Add 100g of cottage cheese
  • Add some chopped onion and garlic
  • Spice it up: salt, pepper, oregano, basil, parsley
  • Add lemon juice made from squeezing one lemon

Take a spoon and squish everything together. Keep squishing and mixing everything in the bowl until you get a spread which you can put on bread or crackers. I personally prefer to eat this spread with rye crackers and tomatoes, but you can experiment and find some other combination that tastes good.

And just remember to brush your teeth after consuming. They’re super smelly as food goes.

Rhonda Patrick on the Nootropic effects of sulforaphane

This excerpt is taken from Rhonda’s recent podcast with Tim Ferriss.

Summary of the main benefits she mentions, in the context of nootropics:

  • Positive effect on mood and alleviated depressive symptoms and reduced anxiety (so far confirmed in mouse models, with a current trial underway to test in humans)
  • Improved short term and spatial memory (so far proven in mice, in the context of conditions that affect memory such as alzheimers)
  • Increase in neurite outgrowth – which is how damaged neurons and synapses repair themeselves from injury

And here’s the full excerpt:

“Getting past all of the usual suspects on our list of nootropics here, the other nootropic that I actually take frequently is SULFORAPHANE! It’s not even usually considered a nootropic by most people but I think it has potential to be considered at least a mild nootropic for a variety of reasons. One of the the best reasons to make this argument is the fact that sulforaphane crosses the blood-brain barrier, at least in mice. This is the first criteria that a substance must meet in order for there to be a compelling argument that it somehow exerts effects on the brain — but, in addition to that, it also affects the activities of the immune system which is now known to affect the brain through a series of lymphatic vessels. this new understanding of the immune system’s ability to interact with the brain also helps to explain why manipulating levels of systemic inflammation has, in clinical trials, been shown to affect feelings of depression either inducing depression in the presence of an artificial increase in activity in the immune system by injecting things like interferons into human trial participants or reducing depression caused by this artificial increase in inflammation through the co-administration of a natural anti-inflammatory, such as eicosapentaenoic acid, better known as the omega-3 fatty acid EPA.

In addition to sulforaphane crossing the blood-brain barrier in mice, the compound has been shown in a couple of randomized, double-blinded, placebo-controlled studies in humans to have one sort of effect or another on brain and behavior. For example, treatment with sulforaphane extracted from broccoli sprouts at doses ranging from about 9 mg to about 25 mg, which is an amount that might be found in around 65 grams of fresh broccoli sprouts on the high end, was able to improve autistic behavior checklist scores by 34% and significantly improved social interaction, abnormal behavior, and verbal communication in young men with autism spectrum disorder. Similarly, some measurable effects have been shown in a small trial of people with schizophrenia.

The fact that sulforaphane is exhibiting clear effects on the brain and behavior of people, such as those with autism spectrum disorder, hints that it might continue to show promise in other areas of cognition too. This is because animal studies have really shown a diversity of very interesting effects that are really just waiting to be replicated in humans.

For example: Sulforaphane has been shown to improve spatial working memory and short term memory in mice in the context of conditions that can affect memory in a deleterious way, such as Alzheimer’s Disease. It has been shown to increase neurite outgrowth, which is how damaged neurons and synapses repair themselves after damage from traumatic brain injury. The effect of sulforaphane on a rodent model of Alzheimer’s Disease in some respects is particularly interesting, because, if we go back to our conversation a little bit earlier about the potential choline may have for mitigating some of the negative effects of this disorder, sulforaphane has also been shown to significantly reduce memory impairment that has been experimentally induced by a drug that works specifically by interfering with the effects of acetylcholine in the nervous system, a drug known as scopolamine.

Sulforaphane was, in this animal trial to which I am referring, able to improve the cholinergic system by increasing acetylcholine levels, decreasing acetylcholine esterase activity, and increasing choline acetyltransferase, which is the enzyme responsible for synthesizing acetylcholine in the hippocampus and frontal cortex. This ties in nicely with some of our discussion earlier about the potential importance of the choline system in cognition. Finally, sulforaphane has been shown to have a positive effect on mood and alleviated depressive symptoms and anxiety as effectively as the antidepressant Prozac in a mouse model of depression and I understand that there is at least one trial currently in the beginning stages looking to confirm this effect in humans as well.

If you consider the variety of brain and behavioral effects demonstrated already in humans, I’m optimistically hoping that some of the groups out there working on these questions will have something good to show for it in the future.”

See the full Tim Ferriss podcast for more info.

And see this post on sulforaphane supplements + info on how to grow broccoli sprouts yourself, which contain the glucoraphanin and myrocinase your body needs to convert into sulforaphane.