W is for White Sugar

Dear everyone,

Processed white sugar is not evil. In fact, I’ve been using it for therapeutic purposes for many years now. When I was withdrawing from Ritalin, I was having 3 – 4 cups of sugar a day. Stress will burn through lots of energy, but it will also eat up your body as well…leading to Cachexia. These days, I have at least 8 tablespoons of white sugar. For those who think it’s evil and I shouldn’t be promoting it, let’s debunk some myths:

1. Sugar is addictive

From the book, “the First Diet” by Sean Bissell:

[…] It would get sickening to eat 3,000 calories of pure sugar for most people, which is 187 teaspoons. Can you imagine eating that much sugar in a day, every day?

The truth of the matter is, sugar isn’t addictive; really great tasting food is addictive–and easy to overeat. Usually really great tasting food contains a combination of sugar, and fat [and salt, and various flavour enhancers, etc]. Think doughnuts, cookies, chocolate, etc. Even foods that don’t have sugar, and instead have a combination of plain old carbohydrates and fat can be addictive. Think potato chips, French fries, pizza, etc. Great chefs [I’d argue that, even more so, food engineers] have created addictive food. Sugar on its own is not addictive; sugar is pretty gross in its purest form.

If people were truly addicted to sugar, they would be going for the pure stuff, and lots of it. Drug addicts don’t want their drugs cut with filler; they want the purest, strongest drugs possible. If true sugar addicts existed, they would not want their sugar watered down in a soda, or mixed in with a cookie–they would be shoveling pure white sugar straight into their mouths. However, people don’t eat sugar straight.

Yep. Have you ever tried to eat a bowl of straight sugar? It’s very hard to finish it. We have satiety signals for sugar, but not for grains. It’s the stretch response, not a satisfaction response (that we get from sugar) that stops us from eating more. Bread/pasta etc we can eat until we physically feel full (a mechanical satiety), but with sugar we feel full via the sweetness and satiety of having glycogen restocked more efficiently (a chemical satiety).

2. Sugar causes Candida

No it doesn’t. See Limited effect of refined carbohydrate dietary supplementation on colonization of the gastrointestinal tract of healthy subjects by Candida albicans: https://www.ncbi.nlm.nih.gov/m/pubmed/10357735/

In fact, if you try to avoid sugar and Candida can’t find any in the gut, it’s going to reach out and get some from your blood, (where your muscles would be breaking down anywhere to create sugar if it’s not getting enough).

Eating sugar and fruit is helpful, rather than harmful as the cultists say, because well nourished yeasts aren’t harmful in the intestine. But starved yeasts need sugar and so they project invasive filaments into the intestinal wall, and can get into the blood stream, at which point – if they aren’t quickly destroyed by white blood cells – they can grow and quickly kill the person. In a typical year, a few people in the world get invasive candida and quickly die, but millions of Americans will insist that they ‘have candida in the bloodstream.’ Eating sugar (fruits, fruit juices) lowers cortisol, keeping the white cells working, helps to increase thyroid, and keeps the yeast from becoming invasive. PUFA (polyunsaturated fatty acids or omega-3 and -6 oils) are yeast stimulants, unlike saturated fats.”  – Lita Lee PhD

Read more here: http://www.thenutritioncoach.com.au/anti-ageing/defending-fruit-and-other-noncomplex-carbs/

3. Sugar is empty calories

White sugar may not have any nutrition, but it’s still fuel. Imagine a bonfire. It’s the fire and to keep it going, it needs nutrients. Sugar keeps your metabolism burning, but the problem is, stress (which could mean all sorts of things) gets in the way and impairs it and people don’t fuel the fire with supporting nutrients. It’s the lack of supporting nutrients in the diet that cause deficiencies, not the sugar itself. More sugar is fine if you have enough supporting nutrients in your diet.

White sugar is also the most least allergenic as it’s been “cleaned.”

The purification of sugar is done mainly by centrifuging, washing away the materials that don’t crystallize, and it’s only the sucrose that crystallizes, so that produces a very pure substance. Charcoal is used to absorb some of the dark material. Although the molasses contains lots of minerals, heating the solution to concentrate it causes chemical changes in the sugar, and some of the metals act as catalysts, producing brown compounds that are allergenic, irritating, and probably toxic. The solutions used for dialysis that contain glucose have been found to contain toxins (thermal degradation products) produced from the glucose during heat sterilization. Many people are concerned about the spontaneous glycation that supposedly happens in the body when sugars react with proteins (though they are really mostly the result of PUFA degradation), but heat browned foods contain large amounts of those, which are still reactive when they eaten. A 1948 article, “Glucose and the unfermentable reducing substances in cane molasses,” by L. Sattler (Adv. Carbohydrate Chem. 3: 113-128) describes the presence of the (Maillard) substances produced by the reaction of glucose and amines from sugar cane. Honey hasn’t been heated, and many of the coloured chemicals in it are beneficial, but some of them can be allergenic, so it’s good to know the source. If it’s manufactured and brown, it’s probably not really safe.” – Ray Peat, PhD

And lastly, being afraid of white sugar is just as bad for your health as avoiding it. Stress changes your gut microbiota, causes difficulties in digestion and raises inflammation. (See, Microbiota alteration is associated with the development of stress-induced despair behavior: https://www.nature.com/articles/srep43859). That’s why food usually digests better in the company of loved ones. So enjoy your food!

For more on debunking sugar myths, check out Antonio Valladares article here —> https://urbanantonio.com/25-things-you-should-know-about-sugar/

Love,

Genevieve ❤️

Advertisements

V is for Vitality

Dear Genevieve,

Always look for things that ADD to your VITALITY rather than subtract. The popular/trendy thing to do is to just cut things out when someone feels like it’s not right for them. If you read every little negative detail or account on something, it’s possible to instil fear in yourself. Your physiology – the way your body responds through pulse, temperature, mood and sleep – your environment, your experiences (past and present), the way you eat, the way you have eaten – and many more factors, all work to produce *your* reaction. So someone else’s’ experience/account probably will be completely different from yours. Don’t let their experience or even your past experience from ruining your experience of a good thing. Find a way to make the good things work for you – sometimes it’s not enough fuel, the timing or just time…

Coffee is one of those things you do not want to or have to cut out! Learn to use it to your advantage. Caffeine is one of the benefits that strongly enhances vitality.

“Often, a woman who thinks that she has symptoms of hypoglycemia says that drinking even the smallest amount of coffee makes her anxious and shaky. Sometimes, I have suggested that they try drinking about two ounces of coffee with cream or milk along with a meal. It’s common for them to find that this reduces their symptoms of hypoglycemia, and allows them to be symptom-free between meals. Although we don’t know exactly why caffeine improves an athlete’s endurance, I think the same processes are involved when coffee increases a person’s “endurance” in ordinary activities.” – Dr Ray Peat

Caffeine is really a “vitamin-like nutrient or adaptogen.” It can stabilise neurons in the brain and when you eat good things your body needs, your body decides whether it’s used for rest or energy. When stressed, coffee allows for rest. When well fuelled and calm, coffee gives energy. It’s structure is very similar to uric acid. It’s a xanthine, so a powerful antioxidant and lowers nitric oxide. Energy relaxes the cells, so when you are healthy, caffeine can cause relaxation. Something, a lot of us aren’t use to…

Caffeine can also:

– Increases progesterone concentration and production (https://www.ncbi.nlm.nih.gov/m/pubmed/10837842/)

– Lowers the incidence of thyroid disease.

– Protects the liver from alcohol and liver damage

– Protects against cancer, including breast cancer and those caused by radiation

– Increases “efficiency of fuel use,” so speeds up your metabolic rate (http://researchpub.org/journal/jcvd/number/early/70.pdf)

– Improves mood

– Inhibits cortisol synthesis (https://www.sciencedirect.com/science/article/pii/S0014579306007538)

– Provides magnesium and vitamin B1

– Improves athletic performance

– Protects against stress induced cell death without interfering with normal cell turnover

– The polyphenals in coffee chelates heavy metals

– Prevents nerve cell death

– Prevents free radical damage

– Prevents Parkinson’s disease

(http://raypeat.com/articles/articles/caffeine.shtml)

And even improves lung development for babies https://mobile.abc.net.au/news/2017-07-15/benefits-of-caffeine-for-premature-babies-long-lasting/8709772?pfmredir=sm and in adults https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123217/

Caffeine is actually so good that it’s similar to thyroid hormone.*

TSH and growth hormone have also been shown to be lowered from it. (When your TSH is high, it means your thyroid isn’t working well) https://www.ncbi.nlm.nih.gov/m/pubmed/6104718/

*(From Haidut from Ray Peat Forums/IdeaLab) There are many studies showing this effect but here is one of the more recently published.

https://www.nature.com/articles/1602901

“…Methods: Twelve healthy, normal weight men (age: 23.7±2.6 years, mean±s.d.) participated in a four-way crossover, randomized, placebo-controlled, double-blind study. Treatments were administered as tablets of 500 mg GTE, 400 mg tyrosine, 50 mg caffeine, or placebo, and were separated by >3-day washout. The acute thermogenic response was measured in a ventilated hood system for 4 h following ingestion. Blood pressure, heart rate (HR), and subjective appetite sensations were assessed hourly and ad libitum EI 4 h post-dose.

Results: Caffeine induced a thermogenic response of 6% above baseline value (72±25 kJ per 4 h, mean±s.e.) compared to placebo (P<0.0001). The thermogenic responses to GTE and tyrosine were not significantly different from placebo. Tyrosine tended to increase 4-h respiratory quotient by 1% compared to placebo (0.01±0.005, P=0.05). Ad libitum EI was not significantly different between treatments but was reduced by 8% (−403±183 kJ), 8% (−400±335 kJ) and 3% (−151±377 kJ) compared to placebo after intake of tyrosine, GTE and caffeine, respectively. No significant difference in haemodynamics was observed between treatments.”

Here is another one that corroborates the first one above. This one also demonstrates the thermogenic effects of 50mg caffeine and shows that doubling the dose to 100mg did not increase that effect further.

https://academic.oup.com/ajcn/article/77/6/1442/4689853

“…Results: The thermogenic responses (increases over the response to placebo) were 3.7%, 4.9%, 7.9%, 6.3%, 8.5%, and 9.8%, respectively, for the gums containing 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg nicotine/mg caffeine (P < 0.05 for all). Adding caffeine to 1 and 2 mg nicotine significantly enhanced the thermogenic response, but changing the caffeine dose (from 50 to 100 mg) did not change the thermogenic effect. None of the combinations changed the respiratory quotient compared with placebo, which indicates that glucose and fat oxidation rates were increased to a similar extent. Side effects occurred only with 2 mg nicotine.”)

With such strong metabolic benefits, know that their will be a cost. Always look for reasons why, rather than discounting a sole substance. Learn to make good things work in a way that are helpful for you.

Further resources here: https://www.functionalps.com/blog/2014/06/04/coffee-done-right-tips-to-help-avoid-coffee-intolerance/

Love,

Genevieve ❤️

U is for Upgrade

Dear Genevieve,

When recovering from anorexia, it is easy to feel ‘huge,’ but so would anybody if they went from 40kg (80lbs) to 60kg (132lbs). Rather than thinking of it as ‘weight gain,’ think of it as ‘weight restoration’ – just one step in recovery on the road to an upgraded YOU.

On the road to recovery, you will need to remember the lessons you have learned. Think of these as your weapons to tackle any relapse. As you get better at remembering each lesson, you will ‘upgrade,’ but the changes will be more felt inside rather than seen.

Lessons 1. Be not concerned about the opinions of others. In a looks driven society, people choose to live their lives through the eyes of what society wants. We reduce ourselves to ‘before and after shots,’ thinking losing weight will make us happier. We look at photos and think, “I want to look like that,’ rather than, “I want to feel like that.” Yet behind all the smoke and mirrors that come with these images on social media are lies, falsity and deception about what it took to achieve such an appearance. There are literally people who brag about having 3000 calories per day, but then are in closed eating disorders groups, saying they are having 1000 calories per day. Yet we strive for these unrealistic ideals. Why? Because ‘fitness,’ and ‘leanness’ mean fitting in; acceptance at the most. But if looking fit/lean mean secretly wrecking ourselves then something is wrong with society. With soaring suicide and depression rates, we must ask ourselves if changing our appearance is really going to make us happy? Are you going to starve yourself, over-exercise or conform to a societal ideal at the cost of your individuality?

Remember, most of the time, most people are too self-absorbed or busy trying to impress or trying to meet social expectations to pay attention to you. If we live our lives through society’s eyes, we become society’s puppet. We reduce ourselves to just our physical appearance, trying to fit in, while simultaneously eroding our sense of self. Instead, we must choose to live life through our own eyes and what we want. Our health should be our focus. Quality of relationships (i.e. social connection and cohesion), a sense of meaning, certainty in our future, sleep, calmness and many other factors that cannot be seen are far greater than external appearance. They affect how we feel more than what we look like, yet are less focused on, as we can’t see them in a ‘before and after’ shot.

Be true to yourself and your health, not society’s norms. Don’t forget who you are on the inside. This is the base of your opinion of yourself. Hold that above anyone else’s’ opinion. Do not define yourself based on your external appearance and the “likes” you get from social media.

People are eating foods they don’t even like to get a body they don’t even like and get ‘likes’ from people who don’t even know them.

They key is to accept yourself for who you are rather than conforming to a broken society. Losing track of this will rob others, and more importantly yourself of the precious gift that is you.

“Self-worth cannot be verified by others. You are worthy because you say it is so. If you depend on others for your value, it is other-worth.” Wayne W. Dyer

Lesson 2. Depression, lack of motivation, fatigue, inability to relax and sleep well and a fixation on food are symptoms of starvation. Chocolate (or cake, insert whatever food here you like) cravings can be a symptom of not enough calories consistently, rather than just a single nutrient deficiency. If you don’t eat enough food, your body will shut down the production of hormones. The state of these hormones will determine our state of mind, along with a bunch of other factors. Eating consistently and balancing blood sugar will help.

 

Lesson 3. “Organs can shrink by up to 40% (aside from the brain which loses 2% max but seems to compartmentalize and lose function.) Loss of organ mass not only contributes to the weight balance, but the ability to metabolize foods. For an example, if one drastically undereats and loses organ mass, then our ability to store and supply glycogen is compromised, and in a starved individual that begins re-feeding, we tend to see an inability to utilise energy, plus a potential caloric excess due to the inhibition of the resting metabolic rate while starving.” – Billy Craig

You have no idea what constitutes weight gain during recovery. It could have been made up of muscle tissue, water and fatty tissues. These are all ideal in a body that needs a fuel supply that is safe. “Fat is supposed to be on our body. It is part of what defines us as humans and makes us aesthetically the way we are. If we gain weight, it is not a sign that we need to stop eating but that our body is under metabolic stress…Your body is simply protecting you from yourself. Once you begin to treat it right, it will do what you want.” – Nathan Hatch

Lesson 5. Thinness does not necessarily equate to being healthy. Being emaciated and malnourished and striving for that is toxic. I was abusing myself with my foolish self-hate and wasting my life on nonsense. No foods or supplements could fix my own self destructive thoughts against myself. You don’t need to “get your body back,’ after weight restoration.  You already have it, and it’s beautiful the way it is, at any weight. Our bodies are just vehicles for us, passing through this time to the next, so with the time we have in them, we might as well treat it with respect and gratitude.

Lesson 6. Listen to your body – this means, eat when hungry, listening to your cravings and resting when tired. This is going to take time to learn. Diet culture has taught us to view calories as a liability, rather than an asset to keep us alive.  Starvation has become a skill. People approach meals with an eye to numbers rather than how satisfied and good they will make us feel takes away the enjoyment. The same approach when it comes to working out takes away the fun.

“Active movement is natural and intuitive in children, they self-regulate really well, and recover really well. They do not decide to exercise, they just play or sit when they desire.” – Billy Craig.

When it comes to working out, consider whether you are doing it for your health or for your ego. Sometimes rest is best. Our culture conditions us to think resting is laziness, when really it is one of the most productive things we can do.

The idea that resting in bed is helpless/lazy is a cultural/social ideology, no doubt while in bed you’re working hard, hopefully prioritizing some available energy to the repair process…and also rationalizing thoughts and ideas.” – Billy Craig

Dolce far niente” – is the Italian phrase for “the sweetness of doing nothing.” Similarly, John Lennon stated, “time you enjoy wasting is not time wasted.” Yet the art of doing nothing – essentially resting – is a foreign concept to many of us. Schedules are usually packed with one commitment after another, hardly giving us space to feel feelings, let alone hunger. Like all arts, it takes time to learn.

If I asked you to learn a new language, you’d understand that it would take a while, yet dieters want to lose weight in 30 days and you seem to have lost the concept that you’ve spent x years digging this whole and it’s going to take a concerted effort to climb back out.” – Billy Craig.

In recovery, it’s so important to focus on the changes that cannot be seen. Even the strengthening of relationships is far more important than a fixation on external appearance. Quality of life is not determined solely on physical appearance, but rather on how we treat ourselves and others. Treating ourselves with compassion will allow us to break free from the prisons created upon ourselves. Sometimes we have to unlearn what we have learned. Sometimes, we just have to do nothing and spend endless days in bed. Though we have been conditioned that giving up control of our weight is a sign that we have really “let go of ourselves,” it is actually the opposite. The greatest form of self-care is just to accept yourself at the stage you are at now and let recovery unfold a day at a time…

 

Love,

 

A Recovering Genevieve

 

T is for Turning the Bitterness to Forgiveness.

Dear Genevieve,

As I walked out the door toward the gate that would lead to my freedom, I knew if I didn’t leave my bitterness and hatred behind, I’d still be in prison.” Nelson Mandela

We are often, our own hardest person to forgive. We often hold ourselves to expectations to high. These expectations from others, and especially from ourselves then go on to overwhelm us. At our own peril, we are just too dang hard on ourselves. And what for? Emotions go on unacknowledged, as we soldier on. We forget to recuperate and recover. Yet ironically, it is from stopping, accepting, acknowledging and most importantly, forgiving that we grow the most.

I often hear people say they miss being their old self and harbor intense interest in making a comeback. However, it is the journey and acknowledgement of feelings that changes them and causes them to be a little more stronger, a little more wiser and a little more empathetic than who they use to be. Thus, the greatest gift they could offer themselves is forgiveness. The gift of forgiveness is the gift of a bridge to allow them to transcend over who they once were, becoming more than their old self. It is growth in the best possible way.

Holding on to who you use to be, will only hurt you. Defining your self-worth in who you use to be, your appearance and or your performance will only hurt you. This is because these things are all bound to change.

Your face will always be in other people’s faces. In this visual and virtual world, there is just no arguing that looks do matter. The trick is not to make it matter the most. Instead we can strive to be, for example, more kinder, more wiser, more creative, more honest and more respectful. How we look, will never be the best measure of who we are. Imagine ourselves as envelopes. Inside it, we may be a very different person. So before you focus on changing your looks, think about whether that would really change you into the best version of you….

You are not your weight, your size, the amount of calories you eat, the amount of money in your bank account and or the amount of likes you get. You will always be more than just numbers. Numbers will never determine your worth.

You have worth in just being alive. You are a worthwhile person. Affirm the statement that, “you are enough.” Through self-acceptance, this statement will grant you forgiveness and peace.

Part of being human involves making mistakes though, so we must learn to accept this. Making mistakes just means you are trying new things, living, taking risks and challenging yourself to be more vulnerable. Vulnerability is a sign of strength. People warm to the vulnerability of others, as it makes them able to relate to the other better. It’s also a pertinent reminder that you are human.

Never forget that: YOUR MISTAKES DO NOT DEFINE YOU. You are simply, practicing being human and learning. Through forgiveness, we rid ourselves of negative thoughts, which opens the door to a more positive life. Positive thoughts lead to a more positive life.

Forgiving ourselves is hard, but once we do and let go, it becomes easier to let go of unhelpful behaviours. We often turn to unhelpful behaviours, as coping mechanisms, for example, food restriction and constantly weighing yourself. The inner pain they temporarily null may cause long term damage.

Instead seek to nurture and be kind to yourself. Watch the way you speak to yourself the most, as you are with you the longest. And each day, do small things that show love, acceptance, care and forgiveness to you. Over time, these are the things that will give you freedom/peace.

You are doing the best you can. You are a worthwhile person. You worth more than your appearance, your achievements and so much more than what others think of you. Most of all, you deserve happiness and that includes all the food.

Let go of the hurt and you’ll see. You’ll see everything you once saw as dull, light up in colors again. Forgive and flourish.

To Forgive is to set a prisoner free and discover that prisoner was you.” – Lewis B Smedes

Love always,

 

A recovered me.

S is for Shake off the Marketing! 

Dear Genevieve, 
Teas/shakes and all sorts of wonderful “healthy” bars are jammed packed with artificial sweeteners, like stevia. 

“Stevia: increases appetite and elevates adrenalin in that it “tastes” sweet but does not provide glucose to the cell when it’s needing it (perpetuating hypoglycemia).http://www.thenutritioncoach.com.au/anti-ageing/defending-fruit-and-other-noncomplex-carbs/

The only shake I endorse is the shaking off of all the marketing that is designed to make us feel like we aren’t good enough. Whether we see it or not, we all are naturally doing our best to cope with our context, with whatever information we have…

Often combined with other special ingredients and taken with a low-protein and low-carbohydrate diet, these products may work for short-term weight loss, but in the meanwhile will leave you about as confused as a fart in a fan factory. (They will also leave you as gassy as one too, due to the hard to digest ingredients.)
For the brain to work it needs enough glycogen, after all it is the most voracious guzzler of sugar. If you’re looking to “detox” your liver, your first requirement is to have a liver in the first place. Your liver is always detoxing, but, secondly, it helps to have enough protein (that’s a minimum of 100 grams for women) to detoxify estrogen and enough carbohydrates, so you can create glucaronic acid and pee out thyroid suppressive hormones. 

Remember, if anything promises a “quick-fix” for a “long term” issue, it probably isn’t worth your long term investment. “Diets” are designed to fail to keep them profitable and when you fail, the diet blames consumers for not being able to stick to it. Your body knows better though and knows it isn’t able to last on these diets. Listen to it – it knows better than these “diets” and will give you certain cues. Your body wants you to listen to it’s physiology, rather than marketing. 

Also, if anything has the word “bikini body” in it, don’t give in. This is marketing preying on people’s insecurities. Everyone is good enough as they are, until the health/fitness/beauty industry feeds us the idea that we aren’t good enough as we are and instil guilt in us for listening to the many physiological cues. We have these cues for a reason and are bound to listen to them. So we must try not to feel guilty when we “binge” after missing a food/food group for so long. Often, it’s because we need it or are in a calorie deficit. Even the word “binge” illicit guilt, when really it’s not a “binge” when we are in a deficit. We are simply restoring our body back to what it needs for that given time to cope with your context. For example, I notice, I will lean towards more foods towards winter to shield myself from the cold temperatures. This craving will go away during summer when it is warmer. It is like gaining a jacket and then gradually taking it off during the warmer months. 

Remember, you are beautiful, whole and wonderful as you are. No one is like you, so you are able to see your own beauty. Difference is beautiful. Celebrate it and celebrate what your body is able to do now, rather than punishing your body and what it can’t do. Gratefulness, after all, is the greatest antidote to stress. 

And on a final note, people usually like people, because they are able to relate to them. It’s not the facade that people create on social media that draws and bonds people together, it’s, well our follies. People are able to relate to each other more for things that go wrong rather than things than go right. Like, most people could not relate to me from the stuff I do in the gym, but they might be able to relate to me hardly buying new gym outfits. Another example would be scenarios like, “hey you dropped your ice cream? I dropped mine too.” Scenarios like these – whether extreme or not – bond people together. As we help each other rebuild, we create bonds strengthened by common experiences and feelings. It’s the stuff we don’t see on social media. That is, the things we don’t reveal to the rest of the world that draws and bonds people to us. So let your downfalls be your pillars of confidence. We all screw up. This just makes you more relatable to others and thus more likeable. 

And if people don’t like you, 99.9% of the time it’s not because of you. Thus, it’s probably not a good idea to take this personally.

Often the harshest person to forgive is yourself. Know that we all make mistakes. Learning from them makes them all worth it and builds you up to be a more compassionate, confident and courageous person. 

Love always,
A recovered me

R is for Reconciliation

Dear Genevieve,

“People are just as wonderful as sunsets if you let them be. When I look at a sunset, I don’t find myself saying, “Soften the orange a bit on the right hand corner.” I don’t try to control a sunset. I watch with awe as it unfolds.”

– Carl Rogers

We usually apply to this to our closest friends, those, which one of my sweetest friends Ania said, “we would go on a military mission on with.” Yet we seldom apply this view to ourselves.

If a friend is hungry, we usually don’t tell them to starve, wait or that they don’t deserve food or anything negative.

Similarly, if a friend is tired we usually don’t tell them to run a five mile block, go on a marathon for the rest of their lives or even not eat, because they “should” be restricting calories or skipped that workout.

A good friend brainstorms with them and helps deploy strategies full of understanding, empathy, wisdom and consolation. Quite simply, we deploy the three scoops of ice cream – compassion, courage and confidence – and lift this person up, however way our imagination leads us.

As Carl Rogers said, “When the other person is hurting, confused, troubled, anxious, alienated, terrified; or when he or she is doubtful of self-worth, uncertain as to identity, then understanding is called for. The gentle and sensitive companionship of an empathic stance… provides illumination and healing. In such situations deep understanding is, I believe, the most precious gift one can give to another.”

So in essence, we do know how to be a good friend. The trick is, applying this to ourselves. Here are some reminders of what a good friend does:

1. Good friends like you as you are. It is through acceptance that we grow.

“The curious paradox is that when I accept myself just as I am, then I can change.” – Carl Rodgers

Good friends are able to read a situation better, as they aren’t so much emotionally involved. More attention may be paid on the way you think and feel. They hear you out and listen. They know the power of listening and take into account your past, your present situation, your goals and your personality (i.e. your context). They view listening as an art and do what editor Gordon Lish, did for, American writer, Raymond Carver. Lish edited Carver’s work in a hugely creative and transformative way, so Carver felt it was worth unpacking his experiences properly. Sympathy and tenderness and holding Carver in the highest regard was at the core of allowing Carver to unpack. Thus, Lish’s editing/suggestions/admissions that he made to help and transform Carver’s narrative was born from the roots of acceptance. He offered different tacts, other ways of viewing things and adding colors (i.e. a sense of gratitude) to what Carver was saying to him. Significantly, all these different techniques were never ultimatums or threats that the other must change or be abandoned. Sincerely, their insight, although it may not be the definitive answer and they’re not saying they know it all, comes straight from the heart and a desire to be on the same team to reach a better destination together. Good friends provide a safe and comfortable place, where the other is free to express all their joy and sorrow without losing their dignity or friend. Good friends are grateful that they may be so special to share in these moments, as they are with the more joyous times of their friend’s life.

2. Good friends without being too flattering, always keep in mind the things we are doing right. When turbulent storms strike, it’s easy for us to lose sight of all our beautiful feathers. A good friend hears, listens and understands the difficulties you are facing, but never loses sights of all your good points. In their minds, roam the memories of your virtues and when you do fail, they look upon your failures with compassion. A good friend reminds us that it’s not the end of the world when we fail. In fact, they remind us that failure is a part of life. From childhood, we have learned to cope with our necessarily imperfect parents (I say this because there is no such thing as a “perfect” parent) with acquired habits. These whether we like it or not, will reliably let us down in adult life. But we aren’t to blame. Sometimes, we make decisions without enough time to fathom the consequences, the full context or know exactly what the future will hold. Our bias decisions may sometimes steer us blindly into the seas of “I have no idea” land. A good friend helps steer us out of that and reminds us that failures are not rare. Messing up are key points of references and helps builds a stronger connection through acceptance and empathy, which is a wonderfully rewarding interaction. Eventually steering out of the storm, allows for the nourishment and further growth of not only yours, but their already beautiful feathers. Our follies never exclude us from their acceptance and love and vice versa. After all, messing up is a general structure that we all follow – some more often than others. Everyone does it, though we don’t always know it.

So in our hearts and in our mind, we know how to be a good friend. It starts by listening to ourselves – our intuitions, our cravings, our feelings – and accepting those as they are now. We may not be perfect, but we are enough. From listening to ourselves, we build trust. Our culture teaches us the opposite for profit. For example, we have phrases, like “cheat day,” “treat yourself,” and assign foods with moral values. This all tends to us make feel guilty for listening to our bodies and our need for rest and food. Children have a remarkable degree of self-regulation and aren’t yet indoctrinated by marketing. They haven’t yet been told in some way or another that they are not good enough by the health/fitness/beauty industry to sell them things. Thus, they know when to rest when tired and they will eat when hungry. Yet as we grow and become conditioned, by our culture and the significant degree of marketing (including the in-your-face and never-ending release of diets designed to fail), we lose track of taking care of ourselves and treating ourselves like we would our best friend. So remember, although your best friend might not always be there for you in person or in real time, you can always be your own. You know how to be a best friend to your best friend. You just have to direct those relevant skills and apply them to the person that probably needs them the most…yourself. This in itself, is the most rewarding reconciliation. 

 Love always,

 

A recovered me.

Q is for Quitting (or Rather NOT Quitting) Sugar

Dear Genevieve,

To quit sugar is to quit creating energy in a way that is harmonious to creating cellular energy. (See the principles of the universal of energy here: http://www.functionalps.com/blog/2014/06/21/universal-principle-of-cellular-energy/).

Just because you can, doesn’t mean you should. The Hippocratic Oath states we should, “first, do no harm…” and that is what you must always take into account. Your safety is everything. If it’s inappropriate, inefficient, unhelpful and or harmful to yourself and or others, it is probably not a good idea. Yet it is the diet culture, which has really painted sugar as the bad guy. Our physiology knows otherwise though and will give us cues by dictating our cravings. (See more on cravings at https://ichooseicecream.wordpress.com/2016/08/21/g-is-for-guide/). We are bombarded by so much information that we can’t be so hard on ourselves for being nervous about enjoying sugar. We even have pills ready at our disposal, claiming to curb sugar/appetite cravings. Yet, we know when an animal is sick that he/she is unwell, yet we sick to curb our appetite, especially our appetite for sugar to benefit our health?

Smiling, laughing and other normal physiological activities tell us that a baby is well. This is just a short way of saying that the trillions of cells making up the baby are well. Similarly, when the baby is sick, it is a short way of saying that some or all of the baby’s cells are sick. When we give medicine to the sick baby (or sick grown-up), our hope is that the medicine will make these sick cells well again. But unfortunately we are not sure.” – Gilbert Ling

Then we have articles and people preaching the benefits of quitting sugar and suddenly feeling so much better, with a loss of appetite, bounds of energy and exaggerated weight loss. Yet, what we don’t realise and what these people most likely do not realize is that these results are short and may be at the expense of a long-term healing process. It’s “the honeymoon period” these people are experiencing and when someone finds something that works for them, even just for the moment, you can bet that they will shout from the rooftops to every person they come in contact with, not knowing that these results may be sustained by STRESS HORMONES. From my personal experience, I have found I can become very talkative when starving and then calm right down and be more pleasant when well-fed.

Fundamentally, stress hormones do exactly as the name states – place stress on the body. Since we were born, heck, since the dawn of time, “our cells primary and preferred energy source” has always been glucose. (See article The Nutrition Coach http://www.thenutritioncoach.com.au/anti-ageing/defending-fruit-and-other-noncomplex-carbs/). When we work against our own physiology, we create cellular stress and that causes a rise in stress hormones. What does this mean?

Well from the book, “Don’t Quit Sugar,” by Cassie Platt, we learn that this results in:

  • Damaged metabolism
  • Weakened digestion
  • Decreased immunity
  • Sexual and reproductive issues
  • Impaired glucose metabolism
  • Sleep issues
  • Accelerated ageing

…and more, which your body will indicate, take note and take care…

SUFFERING IS NOT A REQUIREMENT FOR SUCCESS.

….but what about burning of storage fat as an energy source?

(From: Politics & Science: William Blake and Art’s Relationship to Science. Thanks to Light. See: https://l-i-g-h-t.com/transcript-474 )

Dr. Ray Peat: It’s very stressful to get in that condition for most people. Extreme hypoglycemia is needed and that typically turns on lots of cortisol production and that has many undesirable consequences, but the worst thing is that almost everyone, the older you are the more polyunsaturated fats you have built into your tissue and those being mobilized and oxidized damage practically everything. They interfere with mitochondrial respiration but they also break down and have cause oxidative damage to everything outside as well as inside the mitochondria. So for a 10-year old, it is not so damaging because their tissues are usually not so loaded with polyunsaturated fats but for a 30 or 40 year old, it can be really harmful.

John Barkhausen: Okay, all right. See, somebody used the metaphor of burning fats is like a slow burning log and burning sugar is like burning kindling. How do you – what’s your take on that metaphor?

Dr. Ray Peat: With a good hot fire you don’t get any smoke, burning unsaturated fats you get very toxic smoke.

So the lesson is burning sugar is a clean way to create energy. It is synonymous with having a “youthful metabolism” and it’s not into old age or in a less than optimal metabolic state that we become inefficient in doing so. Do not make this task more challenging for your body. Work with it and not against it. We need carbohydrates and your body will give out cues to indicate this. In fact, if you can’t get carbs, your body will safeguard you by finding and making glucose from non-carbohydrate sources. It can do this in by two ways:

  1. Lipolysis: fat breakdown
  2. Gluconeogensis: protein breakdown (amino acids).That means, yes, your body will catabolise itself and get amino acids from wherever, including your own muscles to turn them into glucose. This prevents you from the consequences of insufficient blood sugar

If you don’t get enough sugar or starch, then you’ll use protein for energy.” – Ray Peat, PhD

To help facilitate this process, balancing your blood sugar must be prioritized. Basically, making sure you are physiologically not stressed/starving at any point of the day will improve your sleep. Ultimately, the result is freedom from being governed by stress hormones and improved sleep. Even though, sometimes you cannot control external stressors, you probably could exert some control over your blood sugar. (Read more here from Functional Performance Systems http://www.functionalps.com/blog/2012/11/16/low-blood-sugar-basics/ ). Balancing blood sugar = lowered stress hormones = better sleep = better health. For me, I find it is not enough to make sure I just balance my blood sugar for one meal, but rather all day for better sleep and thus better health.

But in energy-deprived humans, increases of adrenaline oppose the hibernation reaction, alter energy production and the ability to relax, and to sleep deeply and with restorative effect.” – Dr Ray Peat, PhD (Thyroid, insomnia and the insanities http://raypeat.com/articles/articles/thyroid-insanities.shtml)

Feed your body better and both it and your mind will thank you from the better sleep.

“Yes. The first thing when your blood sugar falls because your liver hasn’t stored enough glycogen to turn into glucose, the first reaction is for adrenaline to increase to try to squeeze more glycogen into your circulation, for your brain primarily. And when the glycogen is absolutely gone, the adrenaline keeps activating the breakdown of fat and provides increased amounts of circulating fats to make up for the lack of sugar. But, after the fat becomes a source of energy, your cells still need some sugar to maintain their basic processes, and so they turn protein into sugar. And to do that, they increase cortisol, which breaks down gland (thymus is the first to go). And the cortisol will eat up your muscle and skin and immune system pretty quickly to feed your heart, lungs and brain, to keep them alive. So every time your blood sugar falls, you’re shifting over to fat metabolism and breaking down protein, so that your muscles are one of the places that store glycogen. So as your muscles get smaller, then more burden is put on your liver to keep your blood sugar steady and that makes your liver progressively suffer, and eventually it gets to the point that your brain isn’t getting either the right energy or the right kind of energy. One of the things that happens with aging, is that we progressively, from the time we are born, at birth, we’re very highly saturated in our fats, because they’ve been formed from glucose in utero. And we can only make saturated, mono-unsaturated and omega-9 unsaturated fats when we’re supplied with either sugar or protein. But once we start eating in the ordinary environment, our tissues start loading up on the polyunsaturateds from the environment. By the time a person is 40, the brain is pretty full of either the arachadonic acid series or, if they have eaten a lot of fish, there will be mostly the long highly unsaturated fats, mostly the DHA type of fish-oil derived omega-3 fats. And even with a pretty average diet, the old person’s brain is very highly biased towards the DHA type fats. And if you look at Parkinson’s Disease, their favorite genetic protein — that some people like to say is the cause of Parkinson’s Disease, synuclein — is the Parkinson’s equivalent of the glutamine repeat of Huntington’s, or the amyloid, or tau fibrils of Alzheimer’s Disease. Each disease tends to have its own protein that goes haywire. In the case of Parkinson’s, it’s the alpha-synuclein . And DHA, the fish type of unsaturated fat, causes the synuclein protein to change to its toxic form that appears in Parkinson’s Disease. And saturated fats can protect against that. in Parkinson’s you can see the role of fat, inclining the brain towards that degenerative change in the protein. And since pretty much everyone in the environment accumulates these highly unsaturated fats, especially in their brain, but in all tissues with aging, by the time you’re 30 or 40, you become more and more susceptible to all of the degenerative, inflammatory diseases, very much in proportion to the unsaturated fats. And you can find the breakdown products corresponding to the seriousness of Alzheimer’s Disease or Huntington’s or Multiple Sclerosis. The specific breakdown products, such as acrolein, which comes largely from the omega-3 fats, the various reactive break-down products show that these unstable fats are breaking down at an increased rate in the degenerative brain conditions.” – Dr Ray Peat, PhD (Politics, Science, Autoimmune and Movement Disorders).

Personally, I’m fuelled primarily by carbohydrates with adequate proteins and fats for my context. I’m fuelled by balance and I’m never gonna give that up. Never going to let sugar down, unless it’s in coffee…note: I function best on at least 400g of carbohydrates a day, with 120g protein, but your mileage may vary….

Recently, I was alerted to an article by Chris Masterjohn on making glucose from fatty acids. See that article here: https://chrismasterjohnphd.com/2012/01/07/we-really-can-make-glucose-from-fatty/

It’s a pertinent reminder that just because we can do something, does not mean we should or it’s helpful. And sometimes, we don’t really know how much we are suffering until we are out of a situation. Like being in a bad relationship with someone – you can become so accustomed to being treated less than what you deserve that you become desensitised and believe that is normal. But it is not until you are out of that situation that you realise how much you weren’t coping or how heavily you relied on stress hormones to sustain you. We are strong, until we do not have to be. The same may be applied to going from low-sugar to incorporating sugar again. At first, we feel guilty for indulging in our own happiness, after periods of putting diet culture first and going against our physiology and our own needs, but soon we will feel relaxation and as we heal, with balance in our mind, homeostasis will manifest in both our body and mind.

Staying true to ourselves and our physiology is what leads to integrity. In truth, we will always be glycogen-guzzling machines. Feeding your cells with the right sugars will lower your stress hormones and you will get the glucose you need to support many functions, including your brain (thinking power. Note: the brain is the most voracious guzzler of glycogen) and the production of thyroid hormone. When we bring it back to physiology and actually listen to our cravings rather than people preaching fake science, we are able to exhibit more compassion to ourselves and others and the world is never short of enough kindness, especially when we have an increasing amount of angry-sugar-craving or just plain-starving people around.

For me, I’m fueled primarily by carbohydrates with adequate proteins and fats for my context. I’m fueled by balance and I’m never gonna give that up. Never going to let sugar down, unless it’s in coffee…note: I function best on at least 400g of carbohydrates a day, with 120g protein, but your own mileage may vary.

Context is everything, and it’s individual and empirical.” – Dr Ray Peat, PhD

In closing, I’d like to add with gratitude, Dr Ray Peat’s response to Chris Masterjohn’s article:

You seem to be getting both mileage and power from your sugar.

Chris Masterjohn has written some good articles on cholesterol, but this one isn’t so good. The fact that, under extreme conditions, some fat is converted into glucose, doesn’t make ketosis less harmful; most of the glucose is still coming from tissue proteins, and the pathway they identify, through methylglyoxal, just helps to explain some of the long-range harm done by ketosis, since methylglyoxal made from the glycerol released when tissue triglycerides are metabolized is (along with acrolein and other lipid peroxidation products) a major factor in the degenerative changes produced by diabetic ketosis, or by the increased free fatty acid metabolism caused by trauma. Any extra methylglyoxal from fatty acid conversion adds to the effect of that from triglyceride metabolism and any from lactic acid, to accelerate aging, autoimmunity, neurological degeneration, etc.

Klin Lab Diagn. 2010 Mar;(3):22-36.

[Methylglyoxal–a test for impaired biological functions of exotrophy and endoecology, low glucose level in the cytosol and gluconeogenesis from fatty acids (a lecture)].

[Article in Russian]

Titov VN, Dmitriev LF, Krylin VA, Dmitriev VA.

Abstract

In philogenesis, due to the failure to store a great deal of carbohydrates in vivo as glycogen, all animal species began synthesizing from glucose palminitic fatty acid and depositing it as triglycerides. During biological dysfunction of exotrophy (long starvation, early postnatality, hibernation), cells also accomplish a reverse synthesis of glucose from fatty acids under aerobic conditions. Under physiological conditions, acetyl-CoA that is converted to malate and pyruvate in the glyoxalate cycle is a substrate of glyconeogenesis. Under pathological conditions of hypoxia and deficiency of macroerges, gluconeogenesis occurs without ATP consumption through the methylglyoxal pathway when used as a substrate of ketone bodies via the pathway: butyric acid (butyrate) –> beta-hydroxybutyrate –> acetoacetate –> acetone –> acetol –> methylglyoxal –> S-D-lactol-glutathione –> D-lactate –> pyruvate –> D-lactate. Under physiological conditions, this gluconeogenesis pathway does not function. We believe that with low glucose levels in the cell cytosole (glycopenia), under pathological conditions of hypoxia and due to failure to mitochondria to oxidize fatty acids, gene expression and gluconeogenesis occur through the methylglyoxal pathway. At the same time, the cytosol, intercellular environment, and plasma shows the elevated levels of methylglyoxal and D-lactate that it is converted to by the action of glyoxalases I and II. Under pathological conditions, glycopenia develops in starvation, diabetes, and metabolic acidosis, neoplasms, renal failure, and possibly, metabolic syndrome. The chemical interaction of methylglyoxal with the amino acid residues of lysine and arginine results in the denaturation of circulating and structurized proteins via carbonylation–glycosylation.

 

Mech Ageing Dev. 2016 Apr;155:48-54.

Novel insights in the dysfunction of human blood-brain barrier after glycation.

Hussain M(1), Bork K(1), Gnanapragassam VS(1), Bennmann D(1), Jacobs K(2),

Navarette-Santos A(2), Hofmann B(2), Simm A(2), Danker K(3), Horstkorte R(4).

(1)Institute of Physiological Chemistry, Martin-Luther-University

Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany.

(2)Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle,

Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.

(3)Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Charitéplatz 1,

10117 Berlin, Germany.

(4)Institute of Physiological Chemistry, Martin-Luther-University

Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany. Electronic

address: ruediger.horstkorte@medizin.uni-halle.de.

The blood-brain barrier (BBB) provides a dynamic and complex interface consisting

of endothelial cells, pericytes and astrocytes, which are embedded in a collagen

and fibronectin-rich basement membrane. This complex structure restricts the

diffusion of small hydrophilic solutes and macromolecules as well as the

transmigration of leukocytes into the brain. It has been shown that carbonyl

stress followed by the formation of advanced glycation endproducts

(AGE=glycation) interfere with the BBB integrity and function. Here, we present

data that carbonyl stress induced by methylglyoxal leads to glycation of

endothelial cells and the basement membrane, which interferes with the

barrier-function and with the expression of RAGE, occludin and ZO-1. Furthermore,

methylglyoxal induced carbonyl stress promotes the expression of the

pro-inflammatory interleukins IL-6 and IL-8. In summary, this study provides new

insights into the relationship between AGE formation by carbonyl stress and brain

microvascular endothelial barrier dysfunction.

 

Diabetes. 2016 Jun;65(6):1699-713.

Methylglyoxal-Induced Endothelial Cell Loss and Inflammation Contribute to the

Development of Diabetic Cardiomyopathy.

Vulesevic B(1), McNeill B(2), Giacco F(3), Maeda K(2), Blackburn NJ(1), Brownlee

M(3), Milne RW(4), Suuronen EJ(5).

(1)Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa,

Ontario, Canada Department of Cellular & Molecular Medicine, University of

Ottawa, Ottawa, Ontario, Canada.

(2)Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa,

Ontario, Canada.

(3)Diabetes Research Center, Departments of Internal Medicine and Pathology,

Albert Einstein College of Medicine, Bronx, NY.

(4)Diabetes and Atherosclerosis Laboratory, University of Ottawa Heart Institute,

Ottawa, Ontario, Canada.

(5)Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa,

Ontario, Canada Department of Cellular & Molecular Medicine, University of

Ottawa, Ottawa, Ontario, Canada esuuronen@ottawaheart.ca.

The mechanisms for the development of diabetic cardiomyopathy remain largely

unknown. Methylglyoxal (MG) can accumulate and promote inflammation and vascular

damage in diabetes. We examined if overexpression of the MG-metabolizing enzyme

glyoxalase 1 (GLO1) in macrophages and the vasculature could reduce MG-induced

inflammation and prevent ventricular dysfunction in diabetes. Hyperglycemia

increased circulating inflammatory markers in wild-type (WT) but not in

GLO1-overexpressing mice. Endothelial cell number was reduced in WT-diabetic

hearts compared with nondiabetic controls, whereas GLO1 overexpression preserved

capillary density. Neuregulin production, endothelial nitric oxide synthase

dimerization, and Bcl-2 expression in endothelial cells was maintained in the

hearts of GLO1-diabetic mice and corresponded to less myocardial cell death

compared with the WT-diabetic group. Lower receptor for advanced glycation end

products and tumor necrosis factor-α (TNF-α) levels were also observed in

GLO1-diabetic versus WT-diabetic mice. Over a period of 8 weeks of hyperglycemia,

GLO1 overexpression delayed and limited the loss of cardiac function. In vitro,

MG and TNF-α were shown to synergize in promoting endothelial cell death, which

was associated with increased angiopoietin 2 expression and reduced Bcl-2

expression. These results suggest that MG in diabetes increases inflammation,

leading to endothelial cell loss. This contributes to the development of diabetic

cardiomyopathy and identifies MG-induced endothelial inflammation as a target for

therapy.

© 2016 by the American Diabetes Association. Readers may use this article as long

as the work is properly cited, the use is educational and not for profit, and the

work is not altered.

 

Mediators Inflamm. 2015;2015:691491.

Role of the RAGE Axis during the Immune Response after Severe Trauma: A

Prospective Pilot Study.

Uhle F(1), Lichtenstern C(1), Brenner T(1), Fleming T(2), Koch C(3), Hecker A(4),

Heiss C(5), Nawroth PP(2), Hofer S(1), Weigand MA(1), Weismüller K(3).

(1)Department of Anesthesiology, Heidelberg University Hospital, 69120

Heidelberg, Germany.

(2)Department of Medicine I and Clinical Chemistry, Heidelberg University

Hospital, 69120 Heidelberg, Germany.

(3)Department of Anaesthesiology and Intensive Care Medicine,

Justus-Liebig-University, 35392 Giessen, Germany.

(4)Department of General and Thoracic Surgery, Justus-Liebig-University, 35392

Giessen, Germany.

(5)Department of Trauma, Hand and Reconstructive Surgery, University Hospital of

Giessen-Marburg GmbH, Campus Giessen, 35392 Giessen, Germany.

BACKGROUND: Severe traumatization induces a complex pathophysiology, driven by

the patient’s own immune system. The initial activation is a result of

damage-associated molecular patterns, which are released from disrupted and dying

cells and recognized by immune receptors, for example, RAGE. In this study we

aimed to evaluate the contribution of the RAGE axis to early and late immune

responses.

METHODS: We enrolled 16 patients with severe trauma together with 10 patients

after major abdominal surgery and 10 healthy volunteers. Blood samples were taken

on admission and every 48 h for a total of 8 days. Plasma concentrations of

various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA.

Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry.

RESULTS: High and transient levels of IL-6 and methylglyoxal characterize the

early immune response after trauma, whereas samples from later time points

provide evidence for a secondary release of RAGE ligands.

CONCLUSION: Our results provide evidence for a persisting activation of the RAGE

axis while classical mediators like IL-6 disappear early. Considering the

immunocompromised phenotype of the monocytes, the RAGE ligands might be

substantial contributors to the well-known secondary stage of impaired immune

responsiveness in trauma patients.

 

Eur J Med Chem. 2016 Oct 21;122:702-22.

Multifunctional diamine AGE/ALE inhibitors with potential therapeutical

properties against Alzheimer’s disease.

Lohou E(1), Sasaki NA(2), Boullier A(3), Sonnet P(1).

(1)Université de Picardie Jules Verne, Laboratoire de Glycochimie des

Antimicrobiens et des Agroressouces, LG2A, UMR CNRS 7378, UFR de Pharmacie, 1 Rue

des Louvels, F-80037, Amiens Cedex 01, France.

(2)Université de Picardie Jules Verne, Laboratoire de Glycochimie des

Antimicrobiens et des Agroressouces, LG2A, UMR CNRS 7378, UFR de Pharmacie, 1 Rue

des Louvels, F-80037, Amiens Cedex 01, France. Electronic address:

andre.sasaki@u-picardie.fr.

(3)Université de Picardie Jules Verne, UFR de Médecine, 1 Rue des Louvels,

F-80037, Amiens Cedex 01, France; INSERM U1088, Centre Universitaire de Recherche

en Santé (CURS), Avenue René Laënnec – Salouel, F-80054, Amiens Cedex 01, France;

CHU Amiens Picardie, Avenue René Laënnec – Salouel, F-80054, Amiens Cedex 01,

France.

An important part of pathogenesis of Alzheimer’s disease (AD) is attributed to

the contribution of AGE (Advanced Glycation Endproducts) and ALE (Advanced Lipid

peroxidation Endproducts). In order to attenuate the progression of AD, we

designed a new type of molecules that consist of two trapping parts for reactive

carbonyl species (RCS) and reactive oxygen species (ROS), precursors of AGE and

ALE, respectively. These molecules also chelate transition metals, the promoters

of ROS formation. In this paper, synthesis of the new AGE/ALE inhibitors and

evaluation of their physicochemical and biological properties (carbonyl trapping

capacity, antioxidant activity, Cu(2+)-chelating capacity, cytotoxicity and

protective effect against in vitro MGO-induced apoptosis in the model AD

cell-line PC12) are described. It is found that compounds 40b and 51e possess

promising therapeutic potentials for treating AD.

Copyright © 2016 Elsevier Masson SAS. All rights reserved.

 

J Physiol Biochem. 2017 Feb;73(1):121-131.

Ferulic acid prevents methylglyoxal-induced protein glycation, DNA damage, and

apoptosis in pancreatic β-cells.

Sompong W(1)(2), Cheng H(3), Adisakwattana S(4)(5).

(1)Department of Clinical Chemistry, Faculty of Allied Health Sciences,

Chulalongkorn University, Bangkok, 10330, Thailand.

(2)Research Group of Herbal Medicine for Prevention and Therapeutic of Metabolic

Diseases, Chulalongkorn University, Bangkok, 10330, Thailand.

(3)Department of Comparative Biomedical Sciences, School of Veterinary Medicine,

Louisiana State University, Baton Rouge, LA, 70803, USA.

(4)Research Group of Herbal Medicine for Prevention and Therapeutic of Metabolic

Diseases, Chulalongkorn University, Bangkok, 10330, Thailand.

sirichai.a@chula.ac.th.

(5)Department of Nutrition and Dietetics, Faculty of Allied Health Sciences,

Chulalongkorn University, Bangkok, 10330, Thailand. sirichai.a@chula.ac.th.

Methylglyoxal (MG) can react with amino acids of proteins to induce protein

glycation and consequently the formation of advanced glycation end-products

(AGEs). Previous studies reported that ferulic acid (FA) prevented glucose-,

fructose-, and ribose-induced protein glycation. In this study, FA (0.1-1 mM)

inhibited MG-induced protein glycation and oxidative protein damage in bovine

serum albumin (BSA). Furthermore, FA (0.0125-0.2 mM) protected against

lysine/MG-mediated oxidative DNA damage, thereby inhibiting superoxide anion and

hydroxyl radical generation during lysine and MG reaction. In addition, FA did

not have the ability to trap MG. Finally, FA (0.1 mM) pretreatment attenuated

MG-induced decrease in cell viability and prevented MG-induced cell apoptosis in

pancreatic β-cells. The results suggest that FA is capable of protecting β-cells

from MG-induced cell damage during diabetes.

 

Int J Mol Sci. 2017 Feb 15;18(2). pii: E421.

Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis.

Wetzels S(1)(2), Wouters K(3), Schalkwijk CG(4), Vanmierlo T(5), Hendriks JJ(6).

(1)Department of Internal Medicine, Cardiovascular Research Institute Maastricht,

Maastricht University, 6229 Maastricht, The Netherlands.

suzan.wetzels@uhasselt.be.

(2)Department of Immunology and Biochemistry, Biomedical Research Institute,

Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium.

suzan.wetzels@uhasselt.be.

(3)Department of Internal Medicine, Cardiovascular Research Institute Maastricht,

Maastricht University, 6229 Maastricht, The Netherlands.

kristiaan.wouters@maastrichtuniversity.nl.

(4)Department of Internal Medicine, Cardiovascular Research Institute Maastricht,

Maastricht University, 6229 Maastricht, The Netherlands.

c.schalkwijk@maastrichtuniversity.nl.

(5)Department of Immunology and Biochemistry, Biomedical Research Institute,

Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium.

tim.vanmierlo@uhasselt.be.

(6)Department of Immunology and Biochemistry, Biomedical Research Institute,

Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium.

jerome.hendriks@uhasselt.be.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system

(CNS). The activation of inflammatory cells is crucial for the development of MS

and is shown to induce intracellular glycolytic metabolism in pro-inflammatory

microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation

endproducts (AGEs) are stable endproducts formed by a reaction of the dicarbonyl

compounds methylglyoxal (MGO) and glyoxal (GO) with amino acids in proteins,

during glycolysis. This suggests that, in MS, MGO-derived AGEs are formed in

glycolysis-driven cells. MGO and MGO-derived AGEs can further activate

inflammatory cells by binding to the receptor for advanced glycation endproducts

(RAGE). Recent studies have revealed that AGEs are increased in the plasma and

brain of MS patients. Therefore, AGEs might contribute to the inflammatory status

in MS. Moreover, the main detoxification system of dicarbonyl compounds, the

glyoxalase system, seems to be affected in MS patients, which may contribute to

high MGO-derived AGE levels. Altogether, evidence is emerging for a contributing

role of AGEs in the pathology of MS. In this review, we provide an overview of

the current knowledge on the involvement of AGEs in MS.

 

Int J Biol Macromol. 2017 May;98:664-675.

Formation mechanism of glyoxal-DNA adduct, a DNA cross-link precursor.

Vilanova B(1), Fernández D(2), Casasnovas R(2), Pomar AM(2), Alvarez-Idaboy

JR(3), Hernández-Haro N(4), Grand A(5), Adrover M(2), Donoso J(2), Frau J(2),

Muñoz F(2), Ortega-Castro J(2).

(1)Department de Química, Institut Universitari d’Investigació en Ciències de la

Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain;

Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca,

Spain. Electronic address: bartomeu.vilanova@uib.es.

(2)Department de Química, Institut Universitari d’Investigació en Ciències de la

Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain;

Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca,

Spain.

(3)Facultad de Química, Departamento de Física y Química Teórica, Universidad

Nacional Autónoma de México, México D.F. 04510, Mexico.

(4)CEA, INAC-SyMMES, F-38000 Grenoble, France.

(5)Univ. Greboble Alpes, INAC-SCIB, F-38000 Grenoble, France; CEA, INAC-SyMMES,

F-38000 Grenoble, France; Universidad Autónoma de Chile, Carlos Antúnez 1920,

7500566, Providencia, Santiago de, Chile.

DNA nucleobases undergo non-enzymatic glycation to nucleobase adducts which can

play important roles in vivo. In this work, we conducted a comprehensive

experimental and theoretical kinetic study of the mechanisms of formation of

glyoxal-guanine adducts over a wide pH range in order to elucidate the molecular

basis for the glycation process. Also, we performed molecular dynamics

simulations to investigate how open or cyclic glyoxal-guanine adducts can cause

structural changes in an oligonucleotide model. A thermodynamic study of other

glycating agents including methylglyoxal, acrolein, crotonaldehyde,

4-hydroxynonenal and 3-deoxyglucosone revealed that, at neutral pH, cyclic

adducts were more stable than open adducts; at basic pH, however, the open

adducts of 3-deoxyglucosone, methylglyoxal and glyoxal were more stable than

their cyclic counterparts. This result can be ascribed to the ability of the

adducts to cross-link DNA. The new insights may contribute to improve our

understanding of the connection between glycation and DNA cross-linking.