Monthly Archives: January 2016

Total Transparency Manifesto

Total Transparency Manifesto

Reference: TTM Website, Leanna Wen TED Talk, Doctor’s Magical Thinking, Doctor’s Paid, Open Payments Database, What Can Patients Do?

Ok, this isn’t about nutrition per se, but they dynamics of health care behind the scenes.   Fundamentally, that had led to many parts of health care being “backwards”, and I wanted to explain that to you. In writing this, I also want to clarify my stance to myself.

Your belief is that your doctor is your advocate, transparent and pure. Many doctors are wonderful, dedicated, caring persons who are your advocate. But they are swimming upstream against powerful forces.   Those powerful forces are not always even evident to them. Let me give you some examples.

Many physicians are subject to review of their practice for meeting quality indicators.   As such, they are incented with bonus pay to meet certain guidelines, established by national committees. When seven panel members of the cholesterol guidelines committee revealed that they had financial ties to statin manufacturers, you get the drift. Now, your doctor may press you with a certain intensity on the need to be on a statin for the reduction of cholesterol.   And you are frustrated because you heard about the Hunt Study from Norway that showed higher cholesterol to not only be harmless, but protective. Then, there is your PCP insisting you be on a statin.   So, you get a cardiac calcium scan and see that you have no calcium. Do you need to be on a statin? No. But your doctor insists. Whose side is your doctor on?   In this context, it is not your own physician at fault, but the very nature of being in a large network of doctors, structured to have financial incentives for clinical work outcomes, based on national guidelines that have been cleverly manipulated to have biased results.   But it’s your doctor who caries it out.

The same conflict shows up in oncology, orthopedics, and on and on, virtually every field.

So, what did Leanna Wen do? As a physician with a mother with breast cancer, she was unsettled on hearing that her mother’s oncologist gave chemo drugs that the oncologist was being paid to speak about publically. She was concerned about possible conflict of interest. She started a simple little project to advocate for total transparency by physicians, and to put that web site up so that everyone could search it. The intent was to create a means by which physicians could pledge that they didn’t have any conflicts of interest, or just what they were. Guess what happened? Well, if you guessed that she was attacked by thousands of angry doctors with floods of email, letters, even calls to her employer to fire her, you would be right.   That is painful to hear.

But that is the world we live in today. Our health care system is designed to be a corporate structure which has to have some profit. Every manager in every health care system in Milwaukee is incented to increase their line of business this year by 4%, so they get their bonus. Milwaukee’s population is not increasing by 4%, so that increase can only come from getting more patients from the other systems, by increasing prices, or by doing more procedures, some of which may not have been necessary. Even Time Magazine has jumped into the fray about breast cancer.

www.WhatWillWork for me. I signed the Total Transparency Manifesto. Ask your doctor if they have. Suggest to them that you think everyone in their network should too. Wouldn’t that give you confidence that your doctor was really on your side?


Pop Quiz


  1. Our health care system pays doctors when you get sick, not to keep you well. T or F


  1. We have designed our health care system to pay handsome sums for procedures, to fix you once you are broken. T or F


  1. We have many national organizations, funded by pharmaceutical companies, that advocate for certain health conditions, that might just be covers for advertising and selling expensive drugs. T or F

That’s it in a nutshell. We should really have a Manifesto for all the advocacy organizations. Ask the Alzheimer’s folks who funds them!

  1. What percent of American doctor’s take some sort of money from health businesses like medical device companies, or pharmaceutical companies?


  1. Would you feel safer if your doctor had taken the Pledge?

You tell me.

FGF21, the Fountain of Youth

FGF21 – The Holy Grail of Longevity

Reference: Youm PNAS 2016, Diabetes, Daily Mail,

We’ve found it!   Ponce de Leon had it wrong. It wasn’t in Florida. They found it at Yale. That’s Connecticut.   Published this last week is another article on FGF21. And it shows how you can add 40 % to the longevity of a mouse.   Well, yes, a mouse. Not a human, but we have much the same physiology and just need to find the equivalent in humans.   It’s there.

Humans have FGF21 too. What is it? Fibroblast Growth Factor 21 is a protein that is produced by the liver in response to a fasting or a ketogenic state.   It does two things that have been known to be linked, but without a clear understanding why. Fasting has been shown to induce longevity by as much as 40% in every mammal ever studied.   And fasting induces your liver to make FGF21.   Fasting also lowers your glucose level, which results in lowering your insulin level. That seems to open the door to the production of FGF21.   That means FGF21 might be the mechanism by which you lose weight too. When you cut calories from carb rich sources, you lower your insulin.   That lowers your sugar levels. And that raises FGF21.

But just how does FGF21 induce longevity? FGF21 comes from your liver. One of the key problems of aging is that our thymus gland gradually stops training T cells to kill off cancers and viruses.   It’s T cells that are out there all over your body checking out cells that don’t quite look right. T cells kill them off and keep you from getting cancer. We want healthy T cell populations. But with aging, you just don’t have them. If you want them, you have to find a way to make more FGF21.   And that’s just what fasting does.

FGF21 is also induced by ketones. That means a state of ketogenesis will increase it. And ketogenesis works when you are eating a diet of fat and very modest protein, but less than 20 grams of carbs a day. And that will explain why the ketogenic diet works in cancer patients. It turns off insulin, a potent growth factor for cancer, and turns on the production of more FGF21. Voila! We thought the ketogenic diet was good for helping weight loss, avoiding Alzheimer’s and improving heart disease risk, but now we can unequivocally add cancer avoidance to the list of reasons to eat a higher fat diet.

There are other FGF proteins which have their own effects.   FGF23 regulates phosphate excretion. FGF15/19 are two similar ones that help regulate glucose metabolism and bile acid excretion. Go figure. And they are secreted in the terminal ileum. (End of your small bowel). And if you want to go down the rabbit hole of physiology, you might enjoy discovering Klotho proteins that help the FGF hormones bind. And how heparin receptors play a part in the nuanced dance of endocrine hormones.

www. What Will Work for Me. This is fascinating to me. We have found the protein hormone that boosts your own immunity. And it works with the same tool we use to fight obesity, heart disease, Alzheimer’s. It’s the human diet.   Now, the new food guidelines came out last week. They made a very timid first step to getting away from carbs and back to fat. They said to cut down on sugar and processed carbs. Finally, a tiny move in the right direction. When they say “load up on butter”, I’ll be proud. Grass raised, by the way. Farmer’s Market is on this winter at the Domes here in Milwaukee. I found some there last week.


Pop Quiz

  1. Ponce de Leon believed there was a fountain of youth in Florida.   All we find in Florida is old people still looking for it.   Where is the fountain?

Inside you. Induced by fasting and a ketogenic diet. FGF21 is its name

  1. Ketones will induce the release of FGF21. What are ketones?

The short pieces of chopped up fat molecules that you burn for energy.

  1. Cancers are slowed down with a ketogenic diet? How?

Probably in part by inducing FGF21 which turns on killer T cells – that kill cancer. In part by turning off insulin, that turns on cancer growth. And lowering glucose, that cancer needs to feast on.

  1. FGF21 is made in the liver, but it’s antiaging effect is most pronounced where?

In your beat up old, senescent thymus gland that isn’t making any T cells anymore.

  1. Humans have been shown to live 40% longer, just like other animals. T or F

Not quite yet. The proof isn’t there quite yet, but as many as 100,000 Americans are living on calorie reduced diets specifically because they believe it. FGF21 may be the key. Stay tuned!

Homocysteine and Metabolic Alzheimer’s

Metabolic Alzheimer’s: Why Homocysteine Matters

Reference:   Bredesen Aging 2015, NEJM 2002, AJCN 2005, Hooshman Neurology 2010

First of all, do you know what Homocysteine is?   It’s a fairly simple concept. It is an amino acid that you have in every cell in your body. It swaps a methyl group back and forth with methionine, and passes it off in a pathway that begins with B12 and folate.   The next step is to make cysteine, and then glutathione.   Glutathione is the ultimate “detox” compound.   You want that to happen efficiently. It converts many compounds in your body to water soluble forms, and able to be excreted. In effect, you are getting rid of “gunk”, metabolic breakdown products.   Homocysteine backs up when you aren’t doing that efficiently enough. Higher levels of homocysteine, in effect, mean you aren’t getting enough B12 and activated folate, both of which are the sources of methyl groups.   And the net effect you see if higher irritation and inflammation in blood vessels and brain. Homocysteine, by itself, isn’t bad. It is just an indicator of how efficiently you are getting rid of “gunk” and how smoothly you are passing on used chemicals.

This is where it turns interesting. Bredesen, at UCLA, has been thinking about Alzheimer’s and finding that there are many paths to a common end. What looks like one disease in it’s final stages, with memory loss and shrinking brains, may in fact be the common endpoint of several distinct pathways.   In his landmark paper (in my humble opinion) he documents the three patterns of Alzheimer’s that he has been observing. The first type might be termed inflammatory with high C-reactive protein and abnormal albumin/globulin ratios: markers of inflammation. The second would be metabolic. This is where diabetes and insulin resistance come in, along with low Vitamin D, low sex hormones and inadequate B vitamins, which shows up with high homocysteine levels. The final type might be called toxic, and affects all parts of the brain, happens to younger folks and is often associated with very low zinc levels. It shows up with slightly different symptoms – not being able to calculate math or find words as well.

How does homocysteine fit in Alzheimer’s?   It has been shown to increase all sorts of pathways that drive the brain pathology of Alzheimer’s. And when measured, it has been shown to have a linear risk associated with it.   This might be the take home lesson.   Having a low homocysteine is highly desirable.   Hooshman in Neurology published a paper showing that homocysteing increases of 1 mg per deciliter resulted in a 16-19% increased risk of Alzheimer’s. Ouch.   And this corroborates earlier studies like Sehsadri in the NEJM that shows a doubling of risk by increases from 7 to 15.   If your level is 15 and you want to make an impact on your future risk for Alzheimer’s, getting your homocysteine down to 7 might be one of the more effective strategies.

And how do you do that? Most of the time, it comes down to more B12 and activated folate.   Remember all those old country doctors that used to give B 12 shots that we ridiculed? Hmmm.   Perhaps they are chuckling in their graves right now.

WWW. What will work for me. This is simple. I already take a B12 supplement. I lowered my homocysteine last year by 3 points and then haven’t measured it since. Going forward, I am adding it to my annual lab panel.


Pop Quiz

  1. Homocysteine is a poison in your body that you want to get rid of?   T or F

False. It is a simple mid-path indicator of metabolic efficiency.

  1. It explains all cases of Alzheimer’s. T or F

False. That would be overreaching. But it may be central to a metabolic explanation of one type.

  1. Lowering your homocysteine might be a critically important means of avoiding Alzheimer’s. T or F

False. Not proven yet. It is an association. But it’s very strong evidence.

  1. My doctor wants to give me B12 shots. Is she crazy?

No, maybe more forward thinking than we thought

  1. I can get B12 from eating a clean, vegan diet. T or F

False. No B12 at all in plants. Have to have animal or specialized yeast extracts.



Pregnanolone: Memory Cure

Pregnanolone and Memory: The Importance of “Neurosteroids”

Reference: Elsevier Science Direct 2014, Life Extension

Published Jan 4, 2016

Ever heard of pregnanolone?   Probably not, and shouldn’t be expected to. But if you are over 50, you likely should know about it. Your body is making much less now than you used to, and that may be part of why you can’t remember why you walked into that room, or where you put your keys. Your memory isn’t as supple as it used to be, and you feel stressed out about it.

Pregnanolone is the first steroid hormone made from cholesterol. It is the first of 6 steps towards making estradiol, another important Neurosteroid, or Progesterone, or Testosterone, all important sex hormones, but also brain hormones. Turns out that our brains make them too, and use them locally.

For memory to occur, you need to stimulate cells. The principal stimulating chemical is called glutamate, and it turns on the NMDA receptor. That’s the beginning of the cascade that puts down new synapses and creates memory. Now, glutamate functions in a very narrow range. Too much glutamate and you get “neuroexictotoxicity” and cell death. That’s the means by which MSG causes brain damage and may be part of the cause of Alzheimer’s and Parkinsons. And that’s where pregnonolone comes it. Not only does it get the memory switch turned on, but it softens the raw damage of too much glutatamate, protecting cells from overstimulation.

The research supporting all this has been done mostly in animals. For example, researchers have shown that pregnanolone reverses impaired learning in older rats. And it happens quickly. It gets even more interesting when you look at anxiety and memory. The side effects of many anti-anxiety medications, like Valium, is that they impair memory. Well, not if you take pregnanolone along with them. And if you want to withdraw from them, pregnanolone may be your best friend, making it easier to do with less rebound anxiety.

The mechanisms of neurosteroids is beginning to be understood. They appear to have a dramatic impact on two areas of brain health. First, they seem to make mitochondria more effective. Mitochondria are the little organs inside the brain cell that make energy molecules. Your brain uses 20% of your bodies energy, so each cell is producing a lot of it. Like our own power plants, producing energy has negative consequences that need amelioration. Reactive oxygen species escape the electron cascade in mitochondria, and need to be soaked up. The neurosteroids appear to help with that.

Pregnanolone also helps with the memory enhancing component of sleep called REM (Rapid Eye Movement) sleep. It increases the time you spend in REM sleep, and upregulates the amount of acetylcholine you make when you do so.

Finally, pregnanolone appears to play a role in building nanotubules inside the brain cell. These tubules appear to be part of the scaffolding that allows new synapses to be constructed and maintained. And that’s the core structure of memory being made. Cool, huh!

WWW. What will work for me. I’m interested in understanding how memory works. I’ve never measured my own levels, but I’m on it. It’s a pretty cheap supplement, and 15 mg a day appears to be the starting dose. Because it’s the parent hormone to many other steroids, there is some concern that it might spark some of the hormone sensitive cancers, but that has not been proven in any fashion. My New Years Resolution is to build a portfolio of memory enhancing ideas for myself, and for you.   Hang on.


Pop Quiz


  1. Pregnanolone is a steroid hormone made in your brain? T or F

True. In your sex organs as well, but also in your brain

  1. It’s levels gradually rise with aging. T or F

False. They drop dramatically

  1. Pregnanolone, and all the neurosteroids, protect the brain from the damaging effects of too much glutamate. T or F

True, and don’t use that to justify eating more MSG

  1. Taking pregnanolone may help withdraw from Valium and other addicting drugs. T or F


  1. Pregnanolone may help your memory by increasing your REM sleep? T or F