Familial hypercholesteromia: Why rely on cholesterol levels when more direct measures are available?

There are two forms of familial hypercholesteromia (FH), namely heterozygous and homozygous FH. In heterozygous FH only one copy of the gene that causes it is present, inherited either from the father or the mother. In homozygous FH, which is the most lethal form, two copies of the gene are present. FH is associated with early-onset cardiovascular disease (CVD).

Homozygous FH may happen if both the father and mother have heterozygous or homozygous FH. If both the father and mother have heterozygous FH, the likelihood that at least one in four children will have homozygous FH will be high. If both parents have homozygous FH the likelihood that all children will have homozygous FH will be high.

In fact, in the latter case, homozygous FH in the children is almost certain. One case in which it won’t occur is if the combining FH gene from the father or mother mutates into a non-FH gene before it is used in the assembly of the genome of the child. A gene mutation in a specific locus, only for the father or mother, is an unlikely event, and would lead to heterozygous FH. Two gene mutations at once in the same locus, for the father and mother, is a very unlikely event.

By the way, despite what many are led to believe based on fictional characters in movies and series like the X-Men and Hulk, mutations in functional genes usually lead to harmful traits. In our evolutionary past, those traits would have been largely removed from the gene pool by selection, making them rare or nonexistent in modern humans. Today we have modern medicine; a double-edged sword.

Mutations leading to super-human traits are very, very unlikely. The myostatin gene, for example, suppresses muscle growth. And yet the mutations that lead to little or no secretion of the related myostatin protein are very uncommon. Obviously they have not been favored by selection, even though their holders are very muscular – e.g., Germany’s “Incredible Hulky” ().

Okay, back to FH. Xanthelasmas are relatively common among those who suffer from FH (see photo below, from Globalskinatlas.com). They are skin deposits of cholesterol, have a genetic basis, and are NOT always associated with FH. This is important – several people have xanthelasmas but not FH.

FH is a fairly rare disease, even in its heterozygous form, with an overall incidence of approximately 0.2 percent. That is, about 1 in 500 people in the general population will have it. Genetically related groups will see a much higher or lower rate of incidence, as the disease is strongly influenced by a genetic mutation. This genetic mutation is apparently in the LDL receptor gene, located on the short arm of chromosome 19.

The table below, from a study by Miltiadous and colleagues (), paints a broad picture of the differences one would typically see between heterozygous FH sufferers and non-FH controls.

The main difference is in total cholesterol and in the relatively large contribution of LDL to total cholesterol. A large difference is also seen in Apolipoprotein B (indicated as "Apo B"), which acts as a LDL transporter (not to be confused with a LDL receptor). The LDL cholesterol shown on the table is calculated through the Friedewald equation, which is notoriously imprecise at low triglyceride levels ().

Looking at the total cholesterol row on the table, and assuming that the numbers after the plus/minus signs are standard deviations, we can conclude that: (a) a little more than two-thirds of the heterozygous FH sufferers had total cholesterol levels falling in between 280 and 446; and (b) a little more than two-thirds of the non-FH controls had total cholesterol levels falling in between 135 and 225.

Keep in mind that about 13.5 percent {calculated as: (95-68)/2} of the non-FH controls had total cholesterol levels between 225 and 270. This is a nontrivial percentage; i.e., these may be a minority but are not rare individuals. Heterozygous FH sufferers are rare, at 0.2 percent of the general population. Moreover, about 2 percent of the non-FH controls had non-pathological total cholesterol levels between 270 and 315. That is not so rare either, amounting to an “incidence” 10 times higher than heterozygous FH.

What would happen if people with heterozygous FH were to replace refined carbohydrates and sugars with saturated fat and cholesterol in their diets? Very likely their already high total cholesterol would go up higher, in part because their HDL cholesterol would go up (). Still, how could they be sure that CVD progression would accelerate if they did that?

According to some studies, the higher HDL cholesterol would either be generally protective or associated with protective factors, even among those with FH (). One of those protective factors may be a more nutrient-dense diet, as many foods rich in cholesterol are very nutrient-dense – e.g., eggs, organ meats, and seafood.

This brings me to my main point in this post. It is mainstream practice to diagnose people with FH based on total and/or LDL cholesterol levels. But the main problem with FH is that it leads to early onset of CVD, which can be measured more directly through simple tests, such as intima-media thickness and related ultrasound plaque tests (). These are noninvasive tests, done in 5 minutes or so, and often covered by insurance.

Even if simple direct tests are not perfect, it seems utterly nonsensical to rely on cholesterol measures to diagnose and treat FH, given the possible overlap between pathological and non-pathological high total cholesterol levels.

Daniel Suelo, the man who quit money, seems remarkably healthy

Daniel James Shellabarger (better known as Daniel Suelo) is portrayed in the bestselling 2012 nonfiction book by Mark Sundeen titled “The Man Who Quit Money” ().

Apparently Suelo stopped using money in 2000, and lives in a cave near the city of Moab in Utah. His diet comprises primarily wild vegetables and fruits, insects, and road kill; as well as discarded or donated food he gets from others when he visits the city. The photo below is from a recent BBC documentary. An interesting 2006 YouTube clip on Suelo is titled “Moneyless in Moab” ().

Suelo is listed as having been born in 1961 (), and the photo above appears to have been taken in 2012. If these dates are correct, he is 51 in the photo above. I cannot help but think that he looks remarkably healthy. The 40-50 age period is one that often sets the stage for many diseases of civilization in urban societies.

Suelo’s decision seems like a radical one, at least to me. There are always complex motivations behind radical decisions. In the case of Suelo, some of these motivations are captured in the comment below, which is part of a review of the book “The Man Who Quit Money” posted on Amazon.com by a reader.

[…] a picture of Suelo not as an untarnished hero, but a man who has wrestled with heartbreak, depression, disillusionment with his family's faith, and his repugnance to working for the pure sake of making money and buying things. Whether or not you are inspired to follow Suelo's example, this book will make you think.

Many people have been inspired by Suelo’s story, to some extent because they see that adopting a radical form of “simple living” () may not only be possible but also liberating. Obviously Suelo’s lifestyle, as it is now, would not be possible without the help of others who adopt a more “traditional” lifestyle. Below is a critical review by a reader of the book, posted on Amazon.com, which harshly reflects this perspective.

Any infantile mentality charmed by this inane story should simply generalize the message - visualize a world in which all of us live like the parasitic protagonist. How fortunate for Suelo that there are still people who engage in productive work and indirectly and unknowingly keep the human sponge alive […] Suelo never quit money he simply quit contributing anything and continues to survive simply as a parasite.

Still, Suelo’s story is interesting, including from a human health perspective. An article on Details.com by Christopher Ketcham provides a glimpse at what a day in Suelo’s life looks like (). It seems that on most days he has one main meal per day.

It is hard to get a sense of the nutrient composition of his diet. It looks like his diet is limited in but not devoid of industrial foods, and one in which food consumption is sporadic, opportunistic, and driven primarily by hunger and availability – not by stress or set meal times, for example.

He probably walks a lot; his cave is one hour away from Moab by foot, and it looks like he goes to Moab often. Apparently he almost never gets sick.

Suelo also writes a blog (), which has many followers, and also maintains other websites, from the Public Library in Moab. His first blog post has over 1,000 comments under it ().

Madonna's "MDNA Show Manifesto" Defends Using Guns on Tour: Do You Agree?

As we speak, Madonna is en route to my city- Philadelphia, to launch the North American leg of her "MDNA World Tour".  In advance of her arrival, she has released a statement to the local Metro defending one of the most controversial parts of her tour...the use of fake firearms in concert.  Here is a portion of that statement:

"It's true there is a lot of violence in the beginning of the show and sometimes the use of fake guns - but they are used as metaphors.  I do not condone violence or the use of guns.  Rather they are symbols of wanting to appear strong and wanting to find a way to stop feelings  that I find hurtful or damaging.   In my case its wanting to stop the lies and hypocrisy of the church,  the intolerance of many narrow minded cultures and societies I have experienced throughout my life and in some cases  the pain I have felt from having my heart broken".

Gun violence is (unfortunately) not a new problem.  However, the topic is quite timely due to increased U.S. media coverage following several mass shootings in the past few weeks- Aurora, CO, Oak Creek, WI, and New York, NY.  The issue of gun violence has reached crisis levels in Philadelphia where Madonna will be performing.  A new open source journalism project called http://guncrisis.org/ "contends that there is an epidemic of homicide by gunfire in Philadelphia and similar cities".  They are seeking solutions.

The solutions being sought by GunCrisis: Philadelphia and others involve taking a public health approach to gun violence.  The recent high profile shootings have produced several well-written pieces about gun violence and what we need to do next:

•  Prompt policy discussions about easy access to ammunition, high-capacity magazines, and assault weapons.
• Use our public health skills to conduct further research into the causes of firearm injuries.
• Examine gun violence as a social disease- one that stems from a society "saturated with guns".

Tell me what you think:

Do you believe that the gun "saturation" goes beyond those in our homes to include those used for entertainment?  E.g., Guns in movies or video games; Madonna's concert props

Is Madonna successful? Does using guns as a metaphorical image help her reach her goals and battle against hypocrisy and intolerance?

In addition to those listed above, what other strategies should we incorporate into a public health approach against gun violence?

The 2012 Atherosclerosis egg study: Plaque decreased as LDL increased with consumption of 2.3 eggs per week or more

A new study by David Spence and colleagues, published online in July 2012 in the journal Atherosclerosis (), has been gaining increasing media attention (e.g., ). The article is titled: “Egg yolk consumption and carotid plaque”. As the title implies, the study focuses on egg yolk consumption and its association with carotid artery plaque buildup.

The study argues that “regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease”. It hints at egg yolks being unhealthy in general, possibly even more so than cigarettes. Solid critiques have already been posted on blogs by Mark Sisson, Chris Masterjohn, and Zoe Harcombe (, , ), among others.

These critiques present valid arguments for why the key findings of the study cannot be accepted, especially the finding that eggs are more dangerous to one’s health than cigarettes. This post is a bit different. It uses the data reported in the study to show that it (the data) suggests that egg consumption is actually health-promoting.

I used the numbers in Table 2 of the article to conduct a test that is rarely if ever conducted in health studies – a moderating effect test. I left out the “egg-yolk years” variable used by the authors, and focused on weekly egg consumption (see Chris’s critique). My analysis, using WarpPLS (), had to be done only visually, because using values from Table 2 meant that I had access only to data on a few variables organized in quintiles. That is, my analysis here using aggregate data is an N=5 analysis; a small sample indeed. The full-text article is not available publicly; Zoe was kind enough to include the data from Table 2 in her critique post.

Below is the model that I used for the moderating effect test. It allowed me to look into the effect that the variable EggsWk (number of eggs consumed per week) had on the association between LDL (LDL cholesterol) and Plaque (carotid plaque). This type of effect, namely a moderating effect, is confusing to many people, because it is essentially the effect that a variable has on the effect of another variable on a third. Still, being confusing does not mean being less important. I should note that this type of effect is similar to a type of conditional association tested via Bayesian statistics – if one eats more eggs, what is the association between having a high LDL cholesterol and plaque buildup?

You can see what is happening visually on the graph below. The plot on the left side is for low weekly egg consumption. In it, the association between LDL cholesterol and plaque is positive – eating fewer eggs, plaque and LDL increase together. The plot on the right side is for high weekly egg consumption. In this second plot, the association between LDL cholesterol and plaque is negative – eating more eggs, plaque decreases as LDL increases. And what is the turning point? It is about 2.3 eggs per week.

So the “evil” particle, the LDL, is playing tricks with us; but thankfully the wonderful eggs come to the rescue, right? Well, it looks a bit like it, but maybe other foods would have a similar effect. In part because of the moderating effect discussed above, the multivariate association between LDL cholesterol and plaque was overall negative. This multivariate association was estimated controlling for the moderating effect of weekly egg consumption. You can see this on the plot below.

The highest amount of plaque is at the far left of the plot. It is associated with the lowest LDL cholesterol quintile. (So much for eggs causing plaque via LDL cholesterol eh!?) What is happening here? Maybe egg consumption above a certain level shifts the size of the LDL particles from small to large, making the potentially atherogenic ones harmless. (Saturated fat consumption, in the context of a nutritious diet in lean individuals, seems to have a similar effect.) Maybe eggs contain nutrients that promote overall health, leading LDL particles to "behave" and do what they are supposed to do. Maybe it is a combination of these and other effects.

Usage Of Henna On Your Hair...

* If you use henna regularly, you will find that the graying of hair will also
   get reduced.

* Take a plastic bowl and take henna in sufficient quantity. Add slightly

   warm water and some lemon juice to it and mix thoroughly so that it

   mixes consistently and becomes a paste. Leave the mixture overnight

   so that the dye works well on hair.

* Add the ingredients properly and if you have dry hair you can add few
   drops of mustard oil to it. For oily hair only lemon juice is sufficient.
   You can add 2 teaspoons of yogurt if you have dandruff in your hair.

* Wash your hair before applying the henna paste. Make sure you wear
   old clothes before applying henna on your hair because it leaves

   black stains.

* You can wear hand gloves so that you can prevent your hands from
   getting stained.

* If you have long hair, you can part your hair from middle and start
   applying the henna paste.  Cover all the parts and apply to the full
   length of your hair.

* Leave the henna applied hair for one or two hours as you need the
   colour to come out and then wash it with running water. Once the paste
   is removed, you can apply a mild shampoo and let the hair dry naturally.

Ancestral Health Symposium 2012: Evolutionarily sound diets and lifestyles may revolutionize health care

The Ancestral Health Symposium 2012 was very interesting on many levels. Aaron Blaisdell and the team of volunteers really did a superb job at organizing the Symposium. Boston is a great city with an excellent public transportation system, something that is always great for meetings, and a great choice for the Symposium. Needless to say, so was Harvard. Even though the program was packed there were plenty of opportunities to meet and talk with several people during the breaks.

We had our panel “New Technologies and New Opportunities”, which Paul Jaminet moderated. The panelists were Chris Keller, Chris Kresser, Dan Pardi, and myself. The first photo below, by Bobby Gill, shows Chris Keller speaking; I am on the far left looking at the screen. The second photo, by Beth Mazur, shows all the panelists. The third photo, also by Bobby Gill, shows a group of us talking to Stephan Guyenet after his presentation.

I talked a bit toward the end of the panel about the importance of taking nonlinearity into consideration in analyses of health data, but ended up being remembered later for saying that “men are women with a few design flaws”. I said that to highlight the strong protective effect of being female in terms of health, which was clear from the model I was discussing.

There is a good evolutionary reason for the protective effect of being female. Evolution is a population phenomenon. Genes do not evolve; neither do individuals. Populations evolve through the spread or disappearance of genotypes. A healthy population with 99 men and 1 woman will probably disappear quickly, and so will its gene pool. A healthy population with 99 women and 1 man will probably thrive, even with the drag of inbreeding depression. Under harsh environmental conditions, the rate of female-to-male births goes up, in some cases quite a lot.

I was able to talk to, or at least meet briefly face-to-face with, many of the people that I have interacted with online on this blog and other blogs. Just to name a few: Miki Ben-Dor, Aaron Blaisdell, Emily Deans, Andreas Eenfeldt, Glenn Ellmers, Benjamin Gebhard, Stephan Guyenet, Dallas Hartwig, Melissa Hartwig, Paul Jaminet, Chris Keller, Chris Kresser, Mathieu Lalonde, Robert Lustig, Chris Masterjohn, Beth Mazur, Denise Minger, Jimmy Moore, Katherine Morrison, Richard Nikoley, Dan Pardi, Kamal Patel, David Pendergrass, Mark Sisson, Mary Beth Smrtic, J. Stanton, Carlos Andres Toro, and Grayson Wheatley.

It would have been nice to have Peter (from Hyperlipid) there, as I think a lot of the attendants are fans. I attended Jamie Scott’s very interesting talk, but ended up not being able to chat with him. This is a pity because we share some common experiences – e.g., I lived in New Zealand for a few years. I did have the opportunity to talk at some length with J. Stanton, who is an inspiration. It was also great to exchange some ideas with my panelists, Miki Ben-Dor, Emily Deans, Stephan Guyenet, Chris Masterjohn, Kamal Patel, and David Pendergrass. I wish I had more time to talk with Denise Minger, who is clearly a very nice person in addition to being very smart. Talking about a smart person, it was also nice chatting a bit with Richard Nikoley; a successful entrepreneur who is in the enviable position of doing what he feels like doing.

I could not help but notice a tendency among some participants (perhaps many, judging from online threads) to pay a lot of attention to how other people looked in a very judgmental way. That person is too fat, his/her face is too red, she/he looks too old etc. So was this supposed to be the Ancestral Health Pageant 2012? There is nothing wrong with looking good. But many people adopt an evolution-inspired lifestyle because they are quite unhealthy to start with. And this includes some of the presenters. It takes time to change one’s health, relapses occur, and no one is getting younger. Moreover, some of the presenters’ ideas and advice may have much more dramatic positive effects on people other than themselves, because of their own pre-existing conditions. The ideas and advice are still solid.

A message that I think this Symposium conveyed particularly well was that an evolutionarily sound diet and lifestyle can truly revolutionize our health care system. Robb Wolf’s talk in particular, based on his recent experience in Nevada with law enforcement officers, made this point very effectively. The title of the talk is “How Markets and Evolution Can Revolutionize Medicine”. One very interesting idea he put forth was that establishments like gyms could expand the range of support activities they offer their customers, officially becoming the beginning of the health care chain. There are already health insurance plans that offer premium reductions for those who go to gyms. Being part of the health care chain would be different and a significant step forward - diet and exercise are powerful "drugs".

One thing that caught me a bit off-guard was Robb’s strong advocacy of the use of a drug, namely metformin (a.k.a. glucophage); even preventively in some special cases, such as with sleep-deprived law enforcement officers. I have to listen to that talk again when it is up online, to make sure that I understood it correctly. It seems to me that changing the nature of shift work among law enforcement officers, at least partially, may be a better target; current practices appear not only to impair the officers’ health but also their effectiveness in law enforcement activities. Besides, I think we need to better understand the nature and functions of cortisol, which is viewed by many as a hormone that exists only to do us harm.

Sleep deprivation is associated with an elevation in cortisol production. Elevated cortisol levels lead over time to visceral fat accumulation, which promotes systemic inflammation. Systemic inflammation is possibly the root cause of most diseases of civilization. But cortisol itself has powerful anti-inflammatory properties, and visceral fat is generally easy to mobilize through intense exercise – probably one of the key reasons why we have visceral fat. I think we need to understand this situation a bit better before thinking about preventive uses of metformin, which nevertheless is a drug that seems to do wonders in the treatment of type 2 diabetes.

Beth Mazur was kind enough to put up a post with links to various Ancestral Health Symposium 2012 summary posts, as well as pictures. Paul Jaminet has a post with an insightful discussion of our panel at the Symposium.

Makeup Tips For Eyes, Lips, And Face

Eye Care Tips

* Potatoes and cucumbers will reduce the appearance of dark
   under-eye  circles.
* To your surprise!! baby shampoos can be used as makeup remover.
* If your cream eye shadow dries out, use a few drops of water or
   mineral oil to soften it up again.
*  For sheen on the eyelids, dab a bit of Vaseline for a pretty
    reflective quality, as well as moisture.

Lip Care Tips

* Apply beetroot juice to lips and cheeks as a stain or mix it with
   honey to make your own lip balm.
* Use eye makeup remover to treat super dry, chapped lips.
   It's a great   nighttime lip treatment!
* Use blush as a lipstick, then use clear gloss or lip balm over it.
   It stays for a long time.

Face Care Tips

* Use an egg white mask for a quick fix for diminishing the
   appearance of pores.
* Papaya mixed with plain yogurt into a paste makes a great
   exfoliating mask for all skin types!
* For a longer lasting foundation try a product with silicone.
  The silicone creates a sweat-proof and smudge resistant second skin.